Table of Contents

Obesity

Epidemiology

Main article: Incidence and prevalence of chronic disease

Obesity rates worldwide have doubled in the last three decades, even as blood pressure and cholesterol levels have dropped, according to several studies published in a 2011 issue of Lancet.1) In 1980, about 5 percent of men and 8 percent of women worldwide were obese. By 2008, the rates were nearly 10 percent for men and 14 percent for women. That means 205 million men and 297 million women were obese. An additional 1.5 billion adults were overweight.

Another team concluded in a recent meta-analysis that if Americans keep gaining weight at the current rate, 75 percent of U.S. adults will be overweight and 41 percent obese by the year 2015. A 2002 paper concluded that “the prevalence of obesity is increasing globally, with nearly half a billion of the world’s population now considered to be overweight or obese.”2)

<html> <div class=“thumb2 tright” style=“width:410px;”><div class=“thumbinner”><a href=“/_detail/home/pathogenesis/diabetesprevalence.gif?id=home%3Apathogenesis%3Aepidemiology” class=“media” title=“home:pathogenesis:diabetesprevalence.gif”><img src=“/_media/home/pathogenesis/diabetesprevalence.gif” class=“mediabox2” alt=“” /></a><div class=“thumbcaption”><strong>A progressive leftward shift in age of onset of the childhood disease has been and continues to be observed in the United Kingdom.</strong> This trend in a progressively earlier onset of diabetes is consistent with data from other countries. <em>Source: Gale</em></div></div></div> </html>

Obesity is likely to continue to increase, and if nothing is done, it will soon become the leading preventable cause of death in the United States.

Youfa Wang, MD, PhD 3)

Poor diet and exercise as the only cause for obesity?

Related article Whole foods

It has been widely hypothesized that a poor diet and a lack of exercise, are driving what the World Health Organization has termed “an obesity epidemic.”

A 2010 Reuters article stated:

After all, the leading causes of death in the developed world – cancer, heart disease, stroke, diabetes – all can be prevented to a large degree with exercise, by avoiding tobacco and by eating less fat and sugar and more fruits and vegetables.

But, a 2010 observational study found that increasing fruit and vegetable intake had a marginal impact on risk of cancer.4) According to the research if Europeans increased their consumption of fruit and vegetables by 150g a day (about two servings, or 40% of the WHO's recommended daily allowance), it would result in a decrease of just 2.6% in the rate of cancers in men and 2.3% in women. Even those who eat virtually no fruit and vegetables, the paper suggests, are only 9% more likely to develop cancer than those who stick to the WHO recommendations.

Further, even some of the most ambitious obesity intervention programs, which have gone to great lengths to increase rates of exercise and improve eating habits of a population, have been failures.

One 1999 $200,000 NIH-funded intervention, known as the Pathways program, was performed on two groups of children. Pathways involved a substantial increase in physical education programs, classes about nutrition, significant reduction in fat and calorie content of all school meals, and several other health related measures - and all as part of a randomized controlled trial, the gold standard in studies. The primary goal of the study was to reduce the rate of body fat in the intervention group, but after the three-year intervention the percent of body fat in both groups was essentially identical.5)

Studies such as these suggest that the official dietary advice given over the last decades do nothing to curb the increase in obesity. But just as the lack of effect of using a 10 day course of penicillin for the treatment of an L-form bacteriaDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria. infection is not evidence of antibiotics not being helpful in the treatment of L-form bacteria, neither is one specific life style intervention evidence of lifestyle measures not having effect.

Other interventions, such as a change in the amount and type of carbohydrate, have shown much greater promise.6) 7) 8) 9) 10) 11) 12)

Attrition was high in most of these studies, as they usually are in any kind of long term diet studies where major diet components are changed. Therefore these studies are just as much a test of the patients’ motivation and the skills of the health professional giving them advice as a pure diet test.

The mechanisms behind the effects of a low carbohydrate, - or a low glycemic, diet on weight loss are generally believed by the authors of the studies foremost to be a result of a reduced insulin secretion. Indeed, insulin administration leads to weight gain13) and insulin suppression leads to weight loss.14)

There could however be other mechanisms at play for the effects of a low-carbohydrate diet, such as changes in the body’s (gut) microbiotaThe bacterial community which causes chronic diseases - one which almost certainly includes multiple species and bacterial forms.. 15)(Note the sharper increase in Bacteriodetes on the low-carbohydrate diet in Figure 1.)

In another study, the relative level of the bacterium Selenomonas noxia in the oral cavity was able to predict obesity with a larger than 98 per cent certainty.16) As infection is the main cause of inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. in the oral cavity, it is interesting to note that a diet devoid of refined carbohydrates significantly reduces markers of gingival inflammation.17)

18) 19) 20) 21) 22)

Restoration of the gastrointestinal mucosal barrier may include dietary changes, treatment of dysbiosis, digestive supports, and anti-inflammatory therapies. .

Evidence of infectious cause

The increase (percentage points) in obesity and overweight in adults was faster than in children (0.77 vs. 0.46–0.49), and in women than in men (0.91 vs. 0.65). If these trends continue, by 2030, 86.3% adults will be overweight or obese; and 51.1%, obese. Black women (96.9%) and Mexican-American men (91.1%) would be the most affected. By 2048, all American adults would become overweight or obese, while black women will reach that state by 2034. In children, the prevalence of overweight (BMI 95th percentile, 30%) will nearly double by 2030. Total health-care costs attributable to obesity/overweight would double every decade to 860.7–956.9 billion US dollars by 2030, accounting for 16–18% of total US health-care costs. We continue to move away from the Healthy People 2010 objectives. Timely, dramatic, and effective development and implementation of corrective programs/policies are needed to avoid the otherwise inevitable health and societal consequences implied by our projections.23)

Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associate with weight loss in obese adolescents. OBJECTIVE: To evaluate the effects of a multidisciplinary obesity treatment programme on fecal microbiotaThe bacterial community which causes chronic diseases - one which almost certainly includes multiple species and bacterial forms. composition and immunoglobulin-coating bacteria in overweight and obese adolescents and their relationship to weight loss. DESIGN: Longitudinal intervention study based on both a calorie-restricted diet (calorie reduction=10-40%) and increased physical activity (calorie expenditure=15-23 kcal/kg body weight per week) for 10 weeks.Participants:Thirty-nine overweight and obese adolescents (BMI mean 33.1 range 23.7-50.4; age mean 14.8 range, 13.0-16.0).Measurements:BMI, BMI z-scores and plasma biochemical parameters were measured before and after the intervention. Fecal microbiota was analyzed by fluorescent in situ hybridization. Immunoglobulin-coating bacteria were detected using fluorescent-labelled F(ab')2 antihuman IgA, IgG and IgM.

RESULTS: Reductions in Clostridium histolyticum and E. rectale-C. coccoides proportions significantly correlated with weight and BMI z-score reductions in the whole adolescent population. Proportions of C. histolyticum, C. lituseburense and E. rectale-C. coccoides dropped significantly whereas those of the Bacteroides-Prevotella group increased after the intervention in those adolescents who lost more than 4 kg. Total fecal energy was almost significantly reduced in the same group of adolescents but not in the group that lost less than 2.5 kg. IgA-coating bacterial proportions also decreased significantly in participants who lost more than 6 kg after the intervention, paralleled to reductions in C. histolyticum and E. rectale-C. coccoides populations. E. rectale-C. coccoides proportions also correlated with weight loss and BMI z-score reduction in participants whose weight loss exceeded 4 kg.

CONCLUSIONS: Specific gut bacteria and an associated IgA response were related to body weight changes in adolescents under lifestyle intervention. These results suggest interactions between diet, gut microbiota and host metabolism and immunity in obesity.24)

Some studies are indicating that immune cells and molecules are important for regulating metabolism—and are dysregulated in obesity.

Microbe Minded: cholesterol, fat & human metabolism

Know your rice and lose weight

**Immune system controls beiging obesity** **Immune system controls beiging obesity**

Obesity and infection

Obesity increases morbidity and mortality through its multiple effects on nearly every human system.

Obesity has a clear but not yet precisely defined effect on the immune response through a variety of immune mediators, which leads to susceptibility to infections.

The available data suggest that obese people are more likely than people of normal weight to develop infections of various types including postoperative infections and other nosocomial infections, as well to develop serious complications of common infections. 25)

Although excess visceral fat is associated with noninfectious inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue., it is not clear whether visceral fat is simply associated with or actually causes metabolic disease in humans. To evaluate the hypothesis that visceral fat promotes systemic inflammation by secreting inflammatory adipokines into the portal circulation that drains visceral fat, we determined adipokine arteriovenous concentration differences across visceral fat, by obtaining portal vein and radial artery blood samples, in 25 extremely obese subjects (mean +/- SD BMI 54.7 +/- 12.6 kg/m(2)) during gastric bypass surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Mean plasma interleukin (IL)-6 concentration was approximately 50% greater in the portal vein than in the radial artery in obese subjects (P = 0.007). Portal vein IL-6 concentration correlated directly with systemic C-reactive protein concentrations (r = 0.544, P = 0.005). Mean plasma leptin concentration was approximately 20% lower in the portal vein than in the radial artery in obese subjects (P = 0.0002). Plasma tumor necrosis factor-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells., resistin, macrophage chemoattractant protein-1, and adiponectin concentrations were similar in the portal vein and radial artery in obese subjects. These data suggest that visceral fat is an important site for IL-6 secretion and provide a potential mechanistic link between visceral fat and systemic inflammation in people with abdominal obesity.26)

Vascular dysfunction

At Department of Medicine, University of Washington, Seattle, May 2007 inquiry into TLR4, a key mediator of innate immunityThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease.:

Abstract Vascular dysfunction is a major complication of metabolic disorders such as diabetes and obesity. The current studies were undertaken to determine whether inflammatory responses are activated in the vasculature of mice with diet-induced obesity, and if so, whether Toll-Like Receptor-4 (TLR4), a key mediator of innate immunity, contributes to these responses. Mice lacking TLR4 (TLR4(-/-)) and wild-type (WT) controls were fed either a low fat (LF) control diet or a diet high in saturated fat (HF) for 8 weeks. In response to HF feeding, both genotypes displayed similar increases of body weight, body fat content, and serum insulin and free fatty acid (FFA) levels compared with mice on a LF diet. In lysates of thoracic aorta from WT mice maintained on a HF diet, markers of vascular inflammation both upstream (IKKbeta activity) and downstream of the transcriptional regulator, NF-kappaBA protein that stimulates the release of inflammatory cytokines in response to infection (ICAM protein and IL-6 mRNA expression), were increased and this effect was associated with cellular insulin resistance and impaired insulin stimulation of eNOS. In contrast, vascular inflammation and impaired insulin responsiveness were not evident in aortic samples taken from TLR4(-/-) mice fed the same HF diet, despite comparable increases of body fat mass. Incubation of either aortic explants from WT mice or cultured human microvascular endothelial cells with the saturated FFA, palmitate (100 micromol/L), similarly activated IKKbeta, inhibited insulin signal transduction and blocked insulin-stimulated NO production. Each of these effects was subsequently shown to be dependent on both TLR4 and NF-kappaB activation. These findings identify the TLR4 signaling pathway as a key mediator of the deleterious effects of palmitate on endothelial NO signaling, and are the first to document a key role for TLR4 in the mechanism whereby diet-induced obesity induces vascular inflammation and insulin resistance.27)

and in March 2007 Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. 28)

Inflammation and diabetes

Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation.

For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-kappaB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold (P<0.05).

Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells. and IL-6 secretion (IL-6, Control: 2.7+/-0.5 vs. LPS: 4.8+/-0.3 ng/ml; P<0.001; TNF-alpha, Control: 1.0+/-0.83 vs. LPS: 32.8+/-6.23 pg/ml; P<0.001).

NF-kappaB inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7+/-0.5 vs. NF-kappaB inhibitor: 2.1+/-0.4 ng/ml; P<0.001).

AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-kappaB was increased in T2DM patients (P<0.05), and TLR-2, TRAF-6, and NF-kappaB were increased in LPS-treated adipocytes (P<0.05).

Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls (r=0.678, P<0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P=0.0395) and serum LPS (reduced by 35%, P=0.0139) in a subgroup of previously untreated T2DM patients.

In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease.. Thus, increased adiposity may increase proinflammatory cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. and therefore contribute to the pathogenic risk of T2DM. 29)

Childhood

Childhood obesity may very well be an infectious disease spread by a common cold virus. This is the finding of a recent study that was published in the journal, Pediatrics. According to the study, Adenovirus-36, as it is known in the scientific community, is directly associated with obese children. The association is found in antibodies produced by the previously-infected children. These antibodies – in association with previous animal studies that have looked at the impact of Adenovirus-36 on adult stem cells to produce more fat cells, that also happen to produce more fat – draw the link between the obesity epidemic and this particular virus.

A virus that can increase the production of certain cells offers certain insights on the dangers of viral infections – particularly when considering the spread of cancer and other chronic diseases. Numerous studies have linked viral infections to chronic-fatigue syndrome, prostate cancer, Parkinson's disease, skin cancer, mouth cancer, and even autism and schizophrenia.

The associations between common viruses and the later onset of serious disease presents both a challenge and an opportunity for the scientific community. The challenge is in understanding the basic underpinnings of viruses in general - and the opportunity is in creating vaccinations that can quite effectively remove these chronic diseases from the broader ecology.

Since obesity is seen as an epidemic on its own accord - with the World Health Organization estimating that there are more than 1 billion overweight adults worldwide – the association with a common cold virus should certainly help in the drive toward a vaccination or toward a more permanent solution

Pediatrics, Sept. 2010

see also Ear infections

Fecal microbiota composition in children may predict overweight.30)

Research

Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. 31)

Adenosine is an endogenous metabolite that is released from all tissues and cells including liver, pancreas, muscle and fat, particularly under stress, intense exercise, or during cell damage. 32)

Here, we report that adenosine level in the cerebrospinal fluid, and hypothalamic expression of A1R, are increased in the diet-induced obesity (DIO) mouse. We find that mice with overexpression of A1R in the neurons of paraventricular nucleus (PVN) of the hypothalamus are hyperphagic, have glucose intolerance and high body weight. Central or peripheral administration of caffeine reduces the body weight of DIO mice by the suppression of appetite and increasing of energy expenditure. We also show that caffeine excites oxytocin expressing neurons, and blockade of the action of oxytocin significantly attenuates the effect of caffeine on energy balance. 33)

Higher zonulin levels are associated with higher waist circumference, diastolic blood pressure, fasting glucose, and increased risk of metabolic diseases 34)

'Western'-style diets, high in fat/sugar, low in fibre, decrease beneficial Firmicutes that metabolise dietary plant-derived polysaccharides to SCFAs and increase mucosa-associated Proteobacteria (including enteric pathogens). 35)

This was of particular interest to us because other research has shown that having more Bacteroidetes may be beneficial because the higher that proportion is, the individual tends to be leaner. With higher Firmicutes, that individual tends to be more obese,“ Holscher said. “We don't know if there is any causality for weight loss, but studies have shown that having a higher fiber diet is protective against obesity. 36) 37)

Weight loss strategy

The best idea may be to plan each meal in two parts.

First, consume the essential part of each meal, containing fresh vegetables and anything else important to your personal needs.

Then take a twenty minute break from eating, after which, consider if at that point you may make a stop until the next meal is due.

38)

Bacteria in the gut produce appetite-suppressing proteins about 20 minutes after a meal

Learn More

Immune cells tweak the body’s metabolism to help control obesity

biological effects

===== Notes and comments =====

not sure why I placed this https://www.marshallprotocol.com/forum11/16602-2.html so took it out pending working on what was i thinking

removed broken link Ear infection

<DiseaseHierarchy>

s265:

Some Bacteria make you Fat, some Thin

Some of you may have noticed my recent citation of several papers from Jeffrey Gordon's lab canvassing the topic of obesity, and how gut microbiota (bacterial flora) seem to be involved in whether we get fat (or get thin, or stay 'normal').

“Fat people harbour 'fat' microbes” https://www.bioedonline.org/news/news.cfm?art=3017 and “An obesity-associated gut microbiome with increased capacity for energy harvest” https://tinyurl.com/2rfrzp PMID: 17183312

Well, this week I had an abstract accepted for presentation at an upcoming conference, Metagenomics 2007, and as the moderators were browsing through the conference website, Janet noticed that Jeffrey Gordon had spoken at the same conference last year, and that the video of that presentation was still online.

The video “It's So Nice to Have a Few Trillion Friends: Exploring the Structure and Functions of Our Human Gut Microbiota and Microbiome, Jeffrey I. Gordon, Washington University of St. Louis” is at https://rpvss.ucsd.edu:8080/ramgen/calit2/metagenomics/gordon.rm

This is a “MUST SEE” video. Please put aside 32 minutes of your time to watch it. You will come away with a new appreciation for the bacteria which live in symbiosis with Homo sapiens.

And as an added bonus, there is a video where W. Ford Doolittle, of Dalhousie University (Canada), argues against the concept of Bacterial species altogether. Another 'must see.' https://rpvss.ucsd.edu:8080/ramgen/calit2/metagenomics/doolittle.rm

Note particularly the “agreement to disagree” during the question and answer session of this latter video. This frank exchange of scientific concepts is something I sorely miss when I am in Clinical Medicine circles, where the instinct is to suppress any thought which conflicts with what one supposes to be 'the consensus'.

So where does Th1 diseaseAny of the chronic inflammatory diseases caused by bacterial pathogens. come into all this? Well, as you know, the VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response. is blocked by the Th1 pathogensThe community of bacterial pathogens which cause chronic inflammatory disease - one which almost certainly includes multiple species and bacterial forms. to protect themselves from the beta-Defensin An antimicrobial peptide found primarily in immune cells and transcribed by the Vitamin D Receptor. and Cathelicidin Family of antimicrobial peptides found primarily in immune cells and transcribed by the Vitamin D Receptor. anti-microbial peptides. Yet these same Defensins are key to controlling the flora in the small intestine (recall the earlier video about Crohn's disease for more info). I don't think I need to remind anybody that the GI tract seems to be abnormal in just about every member of our cohort

Previously I have noted that, dependent on the infectious history of an individual, the microbiota they are carrying around (the 'pea soupThe unique combination of bacterial pathogens (and co-mingling of bacterial genes) which accounts for each individual’s disease presentation.') varies from individual to individual.

Additionally, many of the Th1 co-infections are firmicutes, in any case.

Finally, right at the end of the video, Jeffrey discloses that they were able to take bacterial flora from obese mice, and use them to infect 'normal' mice, turning the normals obese in the process. Oh what a can of worms this opens up…

Note: Mr. Gordon states “the environment inside the uterus is sterile”. This is incorrect. The reason the metagenomic teams haven't made a real medical breakthrough is that they are not adequately skilled in a number of clinical areas we stumbled into. We had the necessity to understand Borrelia, for instance, which has been shown to be transmitted during pre-natal gestation. So we have a slightly different view of things to Jeff.

We are told “you are what you eat” but that is not true, because it ignores that the appetite might well be controlled by another factor, eg, Th1 disease. Jeff Gordon's paper showed that obesity was linked to both gut flora and diet. In particular, certain species of bacteria seemed to be encouraged by high fat or high carb diets. In turn, those species all interact with the rest of the flora to determine the efficiency of digestion. I might say “you are what is eating you” but that would be too flippant.

  • s265

s267 & s268:

Firmicutes and CWD species

I included a link to Prof Doolittle, arguing that species are irrelevant, in the first message of this topic.

'Firmicutes' is a pretty broad brush, certainly inclusive of many of the recognized L-formDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria. 'species', but I would emphasize that 94% of the 'species' that Jeff's group found were not able to be identified.

So it's sort of groping around in the dark, at the species level. At the level of “pea soup” it has now been shown that 'transplanting' the pea-soup from ob/ob mice to sterile mice caused those to also become obese.

What was in that pea soup is probably less important at this point; rather the key is that one's infective microbiota can influence one's weight. Which we all sorta knew before, but now our hunch is backed by some science

Dr. Trevor Marshall, Ph.D.

See also Bacteria implicated in obesity

Here is an interesting article which points really well to macrophage-centric immune changes in obesity: “New method finds networks of genes behind obesity” https://www.reuters.com/article/healthNews/idUSN1645889420080316

Schadt's team, writing in two studies published in the journal Nature, said the diseases of obesity appear to originate in the immune system. “The network is enriched for genes that are involved in macrophages,” Schadt said.

https://www.reuters.com/article/healthNews/idUSN1645889420080316

..Trevor..

Last edited on Mon Mar 17th, 2008 15:50 by Meg Mangin R.N.

filelink Resolving obesity

I think this will happen automatically as your innate immune system fully recovers. Ultimately you will be making the antimicrobial peptidesBody’s naturally produced broad-spectrum antibacterials which target pathogens. under control of hormonal feedback from the GI tract, rather than being overwhelmed by the signals from the infected phagocytes. I suspect that the full complement of antimicrobial peptides will allow effective culling of the nasties.

Many folk on the MP are thin, and some go through thinning periods. But weight fluctuates, and I suspect will not totally normalize until the body totally returns to full health.

At that point, 'the world's your oyster'… and we will probably continue to break paradigms as we develop knowledge about 'healthy aging'…

Dr. Trevor Marshall, Ph.D. 

* s267
* s268

S270:

Members' experiences

I had a weight problem for many years prior to the MP. Here is a 'before and after' picture. ~Meg

Last year I walked at least 2 hours every day and managed to loose a fair bit of weight. Had to give up all that walking on the MP and I was really worried that I would pile the weight back on. Well…first couple of months I lost 4 kg when I changed to a totally low carb diet. Then I slackened on my carbs and quite a few crept back in and I regained the 4 kilos. Now….after a month or so of going back onto the low carb eating I have shed those 4 and 3 others. So…all in all…without any exercise and leading a very sedentary lifestyle…I managed to loose 7 kg in 5 months. ~IngeD

See Will the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. help me lose weight?

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f289:

Will the Marshall Protocol help me lose weight?

Many chronically ill persons are overweight, especially those who have taken prednisone. They are often frustrated in their attempts to lose weight even after they have weaned from prednisone. If you are symptomatic, you may find yourself heading to the refrigerator for comfort making weight loss difficult.

Hormonal imbalance in common in Th1 inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. and this can make it difficult to lose weight. Please see this diagram summarizing some of the key relationships between the body's hormones and 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol..

Managing your ImmunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed. assists in, and helps you to feel well enough to concentrate on weight reduction. Please see Tools to check and if you are having problems feel free to ask on the Board.

This article on Cravings, Overeating, and the Brain Connection supports the theory that carbohydrates are needed to synthesize brain opiates (endorphins) to suppress pain and serotonin to improve mood. This provides one reason why many people report they are comforted by eating carbohydrates.

Since the MP recommends a eating plan that is low in refined sugars and simple carbohydrates, following this recommendation may result in a weight loss. The FOOD TIPS forum contains a post on Carbohydrates which includes tips to satisfy your sweet tooth, and Page: 2 has Helpful hints.

Once you are feeling better, you will be able to increase your activity level. Are there any Guidelines on Exercise & the MP? You can then concentrate your efforts on losing undesired weight.

Until then, it is best to focus all your energies on killing the intracellular bacteria that are at the root of your problems.

See also Fasting and exercise

OBESITY Some Bacteria make you Fat, some Thin

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Patients experiences

These 'before and after' pictures we put together for a press release illustrate that the MP can help people return to their normal weight.

“Thanks to Dr. Bernstein's book on diabetes, I've been able to lower my glucose readings into the mid-80s before and AFTER meals by adjusting what I eat and the quantity of what I eat. I have lost 33 lbs. since my December 20, 2006 MD visit - yeah Dr. Bernstein! and doc was very happy with my glucose readings!” ~captkirk: Bree: A1C, weight etc

-Went to see MP doc yesterday–I've lost 20lbs! The only thing I've done different is the MP. ~Ceredwyn

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s271, 272, 273, 274:

Do regulatory T Cells Contribute to Th1 Skewness in Obesity?

Svec P, Vásárhelyi B, Pászthy B, Körner A, Kovács L, Tulassay T, Treszl A. Research Group of Pediatrics and Nephrology, Hungarian Academy of Sciences, Budapest, Hungary.

BACKGROUND: Recent data suggest that an increased prevalence of interferon-gammaAn inflammatory cytokine which causes extra mast cells to differentiate to monocytes and then to further differentiate into macrophages and dendritic cells. These phagocytes are the most active cells of the immune system and are charged with digesting bacterial pathogens. (IFN-gamma) producing CD4 (+) cells is present in obesity. Regulatory T cells (Tregs) have a strong impact on activation and proliferation of CD4 (+) lymphocytes. Data are not available about Tregs and their possible contribution to chronic mild inflammation in obesity. DESIGN: We investigated the prevalence of Tregs in obese children. We also collected data about dendritic cells and monocytes (so-called antigen presenting cells, APCs), important modulators of Tregs and we determined the cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. production of CD4 (+) lymphocytes, the main target cells of Tregs.

METHODS: Twelve obese children and 10 healthy age-matched controls have been enrolled. For flow cytometric analyses, peripheral blood mononuclear cells were used. We determined the prevalence of Tregs by Foxp3 expression of CD4 (+) cells; prevalence of myeloid and plasmacytoid dendritic cells (DCs); prevalence of tumor necrosis factor (TNF)-alpha and interleukin(IL)-12 producing monocytes; and prevalence of IL-2, IL-4 and IFN-gamma producing CD4 (+) cells. RESULTS: The prevalence of Tregs, DCs, TNF-alpha and IL-12 producing macrophages, IL-2 and IFN-gamma producing CD4 (+) cells was similar in both groups. The prevalence of IL-4 producing CD4 (+) cells was lower in obese children than in healthy controls (p=0.028). The ratio of IFN-gamma (+)/ IL-4 (+) CD4 (+) cells was higher in obese children than in those with normal weight (p=0.046).

CONCLUSIONS: CD4 (+) reactions are polarized toward Th1 direction in obesity. The unaltered number of Treg and APCs suggests that these immune regulator cells do not contribute to altered immune status in obese children. PMID: 17647141 [PubMed - in process]

[filelink] Social networks and obesity

Your Best Friend Can Make You Fat: Researchers WASHINGTON (Reuters) By Maggie Fox, Health and Science Editor

The Spread of Obesity in a Large Social Network over 32 Years Nicholas A. Christakis, M.D., Ph.D., M.P.H., and James H. Fowler, Ph.D. New England Journal of Medicine July 26, 2007

[filelink] Childhood obesity

Nature tops nurture in childhood obesity: study

Thu Feb 7, 2008 2:57pm EST LONDON (Reuters) - Diet and lifestyle play a far smaller role than genetic factors in determining whether a child becomes overweight, according to a British study of twins published on Thursday.

Researchers looking at more than 5,000 pairs of twins wrote in the American Journal of Clinical Nutrition that genes account for about three-quarters of the differences in a child's waistline and weight.

“Contrary to the widespread assumption that family environment is the key factor in determining weight gain, we found this was not the case,” said Jane Wardle, director of Cancer Research UK's Health Behavior Centre, who led the study.

Previous studies have pointed to environmental factors as the main cause of obesity, a major problem worldwide that increases the risk later in life of type-2 diabetes, cancer and heart problems.

The World Health Organization classifies around 400 million people worldwide as obese, including 200 million children under the age of five.

The British team looked at pairs of identical twins who share all their genes and compared their measurements with those of non-identical twins who share only half their genes.

A statistical analysis found that the differences in the children's body mass index and waist circumference were 77 percent attributable to genes and 23 percent due to the environment in which the children were growing up.

BMI is calculated by dividing weight by the square of height.

“These results do not mean that a child with a high complement of 'susceptibility genes' will inevitably become overweight, but that their genetic endowment gives them a stronger predisposition,” the researchers said.

The results suggest that parents whose children are at the greatest genetic risk may need support to make sure they provide a healthy environment, the researchers said.

“This study shows that it is wrong to place all the blame for a child's excessive weight gain on the parents,” the researchers said.

(Reporting by Michael Kahn, Editing by Will Dunham and Tim Pearce)

© Reuters 2007.

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Bacteria Mix in Guts of Babies Predicts Obesity

By Kathleen Doheny HealthDay ReporterFri Mar 7, 11:47 PM ET

FRIDAY, March 7 (HealthDay News) – The mix of bacteria in a baby's gut may predict whether that infant will become overweight or obese later in life, a new study suggests.

Babies with high numbers of bifidobacteria and low numbers of Staphylococcus aureus may be protected from excess weight gain, according to a team of researchers from the University of Turku in Finland.

Their study was published in the March issue of The American Journal of Clinical Nutrition.

The researchers suggested their findings may help explain why breast-fed babies are at lower risk for later obesity, since bifidobacteria are prevalent in the guts of breast-fed babies.

Other studies repeatedly have found that being breast-fed is associated with a reduced risk of excess weight or obesity in childhood, with the risk lowered from 13 percent to 22 percent.

In the new study, researchers evaluated children who had been part of a long-term study to evaluate the effect of probiotics on allergic disease. Probiotics are potentially beneficial bacteria found in foods such as yogurt and in dietary supplements.

The children had been evaluated at birth, five more times before age 2, and then again at ages 4 and 7. The researchers in the original study had also tested for intestinal microbes in fecal samples collected at 6 months and 12 months.

For this latest study, the Finnish researchers selected 49 participants from the larger study – 25 of them were overweight or obese at age 7 years, and 24 were normal weight at the same age.

When they looked at the fecal samples, the average bacterial counts of bifidobacteria when taken at 6 months and 12 months were twice as high in those who were a healthy weight as in those who got heavy.

Those who stayed at a healthy weight also had lower fecal S. aureus levels at 6 months and 12 months than did those who got heavy.

The S. aureus may trigger low-grade inflammation, the authors speculated, and that may also contribute to developing obesity.

In other research, gut bacteria in adults have been found to be altered in obese adults who lost weight. Someday, the Finnish researchers speculated, tinkering with gut flora may help prevent or treat obesity.

The latest study doesn't pinpoint exactly why intestinal bacteria are linked with the development of obesity, said Connie Diekman, director of university nutrition at Washington University in St. Louis and president of the American Dietetic Association.

“The exact role that bacteria in the intestine play in development of obesity is still the subject of much research,” she said, “but the benefits of breast-feeding are clear. Breast-feeding provides not only the proper nutrition for your infant, but it provides benefits that may impact long-term health and weight issues as well.”

However, she added that, “while breast-feeding may play a role in the weight of children, so many other factors influence weight that parents shouldn't ignore good role modeling of healthy food choices, proper portions and regular physical activity. Healthy weight is a combination of factors, and no single issue will be the cause of weight gain or the magic answer to weight loss.”

Another expert who has studied how obesity changes microbes in the gut calls the new study unique, because it collected information over several years and could look for differences in gut microflora. “The finding, that the lean children harbored higher levels of bifidobacteria at younger ages, is very intriguing,” says Ruth Ley, a research assistant professor at Washington University School of Medicine in St. Louis.

Still, she says, research on the role of gut bacteria in regulating body weight is in the very early stages.

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Vitamin D Status and Response to Vitamin D(3) in Obese vs. Non-obese African American Children

Iron is required for growth of bacteria

Obese U.S. Younsters Suffer Iron deficiency: Study

Blood pressure rising among U.S. children….an alarming trend linked to obesity rates.

[filelink] There is no study proving a causal link between lifestyle and obesity.

Pathways: a school-based, randomized controlled trial for the prevention of obesity in American Indian schoolchildren.

Caballero B, Clay T, Davis SM, Ethelbah B, Rock BH, Lohman T, Norman J, Story M, Stone EJ, Stephenson L, Stevens J; Pathways Study Research Group.Am J Clin Nutr. 2003 Nov;78(5):904-5.

In 2004, researchers published the results of lifestyle modification of 1704 children from American Indian Communities in the Southwest USA. For three years, schoolchildren participated in a massive randomized intervention program, designed to examine the effects of a change in dietary intake, an increase in physical activity, classroom curriculum focused on healthy eating and lifestyle, and a family involvement program.

In the end, there was no difference in the adipose composition of the two groups, there was no causal link found between lifestyle and obesity. “The primary aim of the study was to reduce the rate of body fat gain in intervention schools, documented by a significant difference in the rate for the control schools after 3 years. This goal was not reached, and %BodyFat in both groups was essentially identical at the end of the intervention period”

There is no study proving a causal link between lifestyle and obesity. We are told “you are what you eat” but that is not true, because it ignores that the appetite might well be controlled by another factor, eg, Th1 disease.

..Trevor..

This study in toddlers came to the same conclusion as the Pathways study: Physical activity to prevent obesity in young children: cluster randomized controlled trial Reilly JJ, Kelly L, Montgomery C, Williamson A, Fisher A, McColl JH, Lo Conte R, Paton JY, Grant S. BMJ. 2006 Nov 18;333(7577):1041.

Over-riding all the studies is mankind's total failure to reverse the epidemic of childhood obesity. We can quote as many studies as we like, but until the trend is reversed, there can be no definite statements made about causation, one way or the other.

I am 'calling' the causation early, taking a scientific risk, because I understand what the role of the Th1 bacteria is in obesity, I understand exactly the prevalence of sub-clinical Th1 disease in the community (about 25% in new York residents), and because I have had the opportunity to discuss the latest molecular data from Jeff Gordon's lab with his staff.

..Trevor..

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Study Ties Belly Fat to Dementia

By SHIRLEY S. WANG March 27, 2008; Page D6 The Wall Street Journal

People who have more belly fat during middle age, even those considered to be of normal weight, have higher rates of dementia when they reach old age, according to a study in the journal Neurology. The link highlights a body of work showing that health is affected by not just overall body weight but how the weight is distributed.

Too much abdominal fat, which extends into the body cavity around major organs, is known to be a risk factor for cardiovascular disease and diabetes. These new findings, published Wednesday, show that large amounts of belly fat are associated with declining cognitive function as well. “There is something very potent about collecting fat in your belly,” said Rachel Whitmer, lead study author and a scientist at the research division of Kaiser Permanente in Oakland, Calif.

It is possible the link between belly fat and dementia is better explained by some other factor, such as poor diet, that wasn't measured in this study, said P. Murali Doraiswamy, an Alzheimer's researcher and chief of biological psychiatry at Duke University who wasn't involved with the study. Using medical records, researchers examined the belly size of 6,583 middle-age people between 1964 and 1973 and then looked to see whether those same individuals were diagnosed with dementia an average of 36 years later.

They found that just being overweight or obese nearly doubles one's risk of dementia in old age, even after taking into account other risk factors such as diabetes and heart disease. But having high levels of central-body fat increases the risk more, boosting an obese person's risk 3.6 times higher than a normal-weight individual with low belly fat. And, as a group, normal-weight individuals with high levels of belly fat showed an elevated risk of dementia.

“It's really a red flag for all of us boomers,” said Duke's Dr. Doraiswamy. “Waist size may not be reflective of just your heart health, but your brain function decades later.” However, Dr. Doraiswamy said there was more variability in the normal-weight group compared with heavier subjects, suggesting that some normal-weight people may be more vulnerable to dementia than others, perhaps due to a genetic predisposition.

This study didn't look at genetic risk, he said. Why belly fat appears to wreak such havoc on the body isn't completely understood. Fat is known to produce a variety of potentially harmful substances that cause inflammation, disrupting blood flow to the heart and possibly the brain, which could be one reason for its link to dementia, said Jean-Pierre Despres, director of research at the Quebec Heart Institute at Laval University in Quebec City, who wasn't involved in the study.

More research is needed to figure out the exact mechanisms of action, he and other experts said. The study wasn't able to examine whether people who lost weight during the 30-year time period decreased their risk of developing dementia, but it is an area of research interest, said study author Dr. Whitmer. Much of where an individual accumulates fat is genetically determined, but abdominal fat is easier to lose than fat stored elsewhere. “This is not a stubborn fat,” Dr. Whitmer said. “It is a toxic fat.”

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J Intern Med. 2010 Jul 29. [Epub ahead of print]

Not a simple fat-soluble vitamin: changes in serum 25-(OH)D levels are predicted by adiposity and adipocytokines in older adults.

Ding C, Parameswaran V, Blizzard L, Burgess J, Jones G.

From the Menzies Research Institute, University of Tasmania, Hobart, Tas.

Abstract

Abstract. Ding C, Parameswaran V, Blizzard L, Burgess J, Jones G (Menzies Research Institute, University of Tasmania, Hobart, Tas.; Monash University, Melbourne, Vic.; Royal Hobart Hospital, Hobart, Tas., Australia). Not a simple fat soluble vitamin: changes in serum 25-(OH)D levels are predicted by adiposity and adipocytokines in older adults. J Intern Med 2010; doi: 10.1111/j.1365-2796.2010.02267.x. Objective. To determine the associations between body adiposity and change in serum 25-(OH)D levels over 2.6 years, and if these associations are mediated by metabolic and inflammatory factors in older adults. Methods. This is a longitudinal study of 859 randomly selected subjects (mean 62 years, range 51-80, 49% women). Serum 25-hydroxyvitamin D [25-(OH)D] was assessed by radioimmunoassay at baseline and 2.6 years later. Baseline serum level of leptin was assessed by radioimmunoassay and interleukin (IL)-6 by a chemiluminescent immunoassay in the first 183 subjects. Results. In multivariable analyses, body mass index, trunk fat percentage and waist-to-hip ratio were significant predictors of increased incident vitamin D deficiency [a 25-(OH)D < 50 nmol L(-1) at follow-up when >/=50 nmol L(-1) at baseline] and decreased recovery of vitamin D deficiency [a 25-(OH)D >/= 50 nmol L(-1) at follow-up when < 50 nmol L(-1) at baseline]. Change in 25-(OH)D levels per annum was also independently predicted by baseline leptin (beta: -0.09/unit, 95% CI: -0.17, -0.03), IL-6 (beta: -0.68/quartile, 95% CI: -1.35, -0.02) and total cholesterol/high-density lipoprotein (HDL) ratio (beta: -0.51, 95% CI: -0.88, -0.14). The associations between body adiposity measures and change in 25-(OH)D completely disappeared after adjustment for leptin, diminished after adjustment for IL-6, but remained unchanged after adjustment for total cholesterol/HDL ratio. All associations were independent of season and sun exposure. Conclusions. Body fat is not simply a passive reservoir for 25-(OH)D. In addition to season and sun exposure, 25-(OH)D levels appear to be determined by metabolic and, to a lesser extent, inflammatory factors, and these appear to mediate the effects of adiposity on change in 25-(OH)D.

PMID: 20804516

Balamurugan, R., G. George, et al. (2010). “Quantitative differences in intestinal Faecalibacterium prausnitzii in obese Indian children.” Br J Nutr 103(3): 335-338. 39)

Gut bacteria contribute to energy conservation in man through their ability to ferment unabsorbed carbohydrate. The present study examined the composition of predominant faecal microbiota in obese and non-obese children. The participants (n 28) aged 11-14 years provided fresh faecal samples and completed a dietary survey consisting of 24 h diet recall and a FFQ of commonly used foods taken over the previous 3 months. Faecal bacteria were quantitated by real-time PCR using primers targeted at 16S rDNA. Of the participants, fifteen (seven female) were obese, with median BMI-for-age at the 99th percentile (range 97 to>99) while thirteen participants (seven female) were normal weight, with median BMI-for age being at the 50th percentile (range 1-85). Consumption of energy, carbohydrates, fat and protein was not significantly different between the obese and non-obese participants. There was no significant difference between the two groups in faecal levels of Bacteroides-Prevotella, Bifidobacterium species, Lactobacillus acidophilus group or Eubacterium rectale. Levels of Faecalibacterium prausnitzii were significantly higher in obese children than in non-obese participants (P = 0.0253). We concluded that the finding of increased numbers of F. prausnitzii in the faeces of obese children in south India adds to the growing information on alterations in faecal microbiota in obesity.

The Human Visceral Fat Depot Has a Unique Inflammatory Profile40)

Obesity can be considered as a low-grade inflammatory condition, strongly linked to adverse metabolic outcomes. Obesity-associated adipose tissue inflammation is characterized by infiltration of macrophages and increased cytokine and chemokine production. The distribution of adipose tissue impacts the outcomes of obesity, with the accumulation of fat in visceral adipose tissue (VAT) and deep subcutaneous adipose tissue (SAT), but not superficial SAT, being linked to insulin resistance. We hypothesized that the inflammatory gene expression in deep SAT and VAT is higher than in superficial SAT. A total of 17 apparently healthy women (BMI: 29.3±5.5 kg/m2) were included in the study. Body fat (dual-energy X-ray absorptiometry) and distribution (computed tomography) were measured, and insulin sensitivity, blood lipids, and blood pressure were determined. Inflammation-related differences in gene expression (real-time PCR) from VAT, superficial and deep SAT biopsies were analyzed using univariate and multivariate data analyses. Using multivariate discrimination analysis, VAT appeared as a distinct depot in adipose tissue inflammation, while the SAT depots had a similar pattern, with respect to gene expression. A significantly elevated (P < 0.01) expression of the CC chemokine receptor 2 (CCR2) and macrophage migration inhibitory factor (MIF) in VAT contributed strongly to the discrimination. In conclusion, the human adipose tissue depots have unique inflammatory patterns, with CCR2 and MIF distinguishing between VAT and the SAT depots.

Basseri, R. J., B. Basseri, et al. (2010). Intestinal Methane Production in Obese Humans Is Associated With Higher Body Mass Index. Digestive Disease Week (DDW) 2010. New Orleans, LA.

Recent evidence has demonstrated that gut bacterial composition may be a factor in the determination of obesity in humans. Simultaneous results have emerged demonstrating a role of methanogenic bacteria in the slowing of intestinal transit in C-IBS and constipation. In follow up study, methane gas directly slowed small bowel transit time. The aim of this study was to investigate the role methane organisms in obesity, since slowing of transit increases intestinal absorption time. Methods: Consecutive subjects were prospectively recruited from a tertiary care obesity center. Subjects were included with a body mass index (BMI) ≥30 at the time of enrollment. After exclusion criteria were applied, subjects completed a symptom questionnaire (VAS scores for bowel symptoms, medications and medical history) and provided a single end expiratory breath sample. Subjects were categorized as methane positive (methane concentration ≥3 parts per million) or methane negative after breath samples were analyzed via a Quintron SC gas chromatograph (Quintron Instrument Company, Milwaukee, WI). Bivariate and multivariate analyses were assessed for associations between BMI, methane, demographics, GI symptoms, prior diagnoses, and medications taken within the last 2 months. Results: A total of 58 patients (74% female) qualified for enrollment. Of these, 12 (20.7%) were categorized as methane positive with a mean breath methane concentration of 12.2±3.1 parts per million. Based on bivariate analysis, the BMI was significantly greater in methane positive subjects (45.3±8.3 kg/m2) compared to methane negative subjects (38.5±5.6 kg/m2) (P=0.001). As in a previous study, methane was associated with a greater severity of constipation on VAS (21.3±6.4 versus 9.5±2.4 in methane negative subjects) (P=0.043). Based on a multiple regression analysis, methane, constipation and antidepressant use were found to be significantly associated with BMI. Since methane and constipation were already known to be collinear, regression analysis was conducted in two ways. In the regression model, controlling for antidepressant use, methane was still an independent predictor of elevated BMI (P<0.001). Interestingly, in the second model, methane was still associated with a 6.55 kg/m2 higher BMI even after controlling for both antidepressant use and constipation (P=0.002). In this model constipation was no longer significant. Conclusions: This is the first study demonstrating that the presence of methanogenic bacteria (as determined by breath test) is a predictor of higher BMI in obese subjects. This is true even when controlling for constipation (as a surrogate symptom of transit).

Zhang, H., J. K. DiBaise, et al. (2009). “Human gut microbiota in obesity and after gastric bypass.” Proc Natl Acad Sci U S A 106(7): 2365-2370. 19164560

Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H(2)-producing bacteria with relatively high numbers of H(2)-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H(2) transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.

Diabetes. 2007 Jul;56(7):1761-72. Epub 2007 Apr 24. Metabolic endotoxemia initiates obesity and insulin resistance.41)

Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmée E, Cousin B, Sulpice T, Chamontin B, Ferrières J, Tanti JF, Gibson GR, Casteilla L, Delzenne NM, Alessi MC, Burcelin R. Institute of Molecular Medicine, I2MR Toulouse, France. Comment in: Diabetes. 2007 Dec;56(12):e20; author reply e21. J Hepatol. 2008 Jun;48(6):1032-4. Abstract Diabetes and obesity are two metabolic diseases characterized by insulin resistance and a low-grade inflammation. Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal endotoxemia increased or decreased during the fed or fasted state, respectively, on a nutritional basis and that a 4-week high-fat diet chronically increased plasma LPS concentration two to three times, a threshold that we have defined as metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain were increased to a similar extent as in high-fat-fed mice. In addition, adipose tissue F4/80-positive cells and markers of inflammation, and liver triglyceride content, were increased. Furthermore, liver, but not whole-body, insulin resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of the LPS and high-fat diet-induced features of metabolic diseases. This new finding demonstrates that metabolic endotoxemia dysregulates the inflammatory tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14 system sets the tone of insulin sensitivity and the onset of diabetes and obesity. Lowering plasma LPS concentration could be a potent strategy for the control of metabolic diseases. PMID: 17456850

Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84. Epub 2007 Jan 8. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.42)

Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Center for Genome Sciences and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63108, USA. Abstract The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. Given the worldwide epidemic in obesity, there is interest in how interactions between human and microbial metabolomes may affect our energy balance. Here we report that, in contrast to mice with a gut microbiota, germ-free (GF) animals are protected against the obesity that develops after consuming a Western-style, high-fat, sugar-rich diet. Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid oxidation (acetylCoA carboxylase; carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose expression is normally selectively suppressed in the gut epithelium by the microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/- animals exhibit similar levels of phosphorylated AMPK as their wild-type littermates in liver and gastrocnemius muscle, they have reduced expression of genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc-1alpha) and enzymes involved in fatty acid oxidation. Thus, GF animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1alpha; and (ii) increased AMPK activity. Together, these findings support the notion that the gut microbiota can influence both sides of the energy balance equation, and underscore the importance of considering our metabolome in a supraorganismal context. PMID: 17210919

«Donna posted in obesity thread: According to senior author Andrew Gewirtz, PhD, associate professor of pathology and laboratory medicine at Emory University School of Medicine, “People are getting obese because they’re eating more, but it suggests the reason they’re eating more may not simply be that calories are cheap and available. The reason they’re eating more may be an increased appetite resulting from changes in intestinal bacteria.”

https://www.wlshelp.com/news/intestinal-bacteria-can-contribute-to-obesity/#more-226

https://www.eurekalert.org/pub_releases/2010-03/eu-ibd030110.php

Good find, Donna. This goes beyond the earlier work with Gordon's group and links obesity to different species within the Firmicutes and Bacteroidetes and to a specific immune dysfunction (TLR5 deficiency).

Joyce Waterhouse

Science. 2010 Apr 9;328(5975):228-31. Epub 2010 Mar 4. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.

Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT. Department of Pathology, Emory University, Atlanta, GA 30322, USA. Comment in: Cell Metab. 2010 May 5;11(5):345-6. Science. 2010 Apr 9;328(5975):179-80. Abstract Metabolic syndrome is a group of obesity-related metabolic abnormalities that increase an individual's risk of developing type 2 diabetes and cardiovascular disease. Here, we show that mice genetically deficient in Toll-like receptor 5 (TLR5), a component of the innate immune system that is expressed in the gut mucosa and that helps defend against infection, exhibit hyperphagia and develop hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity. These metabolic changes correlated with changes in the composition of the gut microbiota, and transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients. Food restriction prevented obesity, but not insulin resistance, in the TLR5-deficient mice. These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome. PMID: 20203013

Obesity: a complex growing challenge. by Pataky Z, Bobbioni-Harsch E, Golay A Related Articles Obesity: a complex growing challenge.

Exp Clin Endocrinol Diabetes. 2010 Jul;118(7):427-33

Authors: Pataky Z, Bobbioni-Harsch E, Golay A

The prevalence of overweight and obesity is increasing worldwide. The physiological mechanisms involved in body weight regulation are complex and incompletely understood. Increasing evidence suggests that obesity is a multifactorial disease where many, if not all, organs of the body are involved. The adipose tissue was considered as a simple fat accumulation for a long period of time. However, nowadays it is fascinating to progressively discover its involvement in hormonal, inflammatory or immune system dysregulation. Adipokines and cytokines are involved in control and regulation of appetite and energy balance, glucose and lipid metabolism, neuroendocrine function, reproduction, immunity, and cardiovascular function. The inflammatory background associated with obesity is closely related to insulin resistance. Moreover, the inhibitory effect of endocannabinoids on the expression of adiponectin could be involved in insulin resistance. Gut microbiota related factor may be responsible for the development of diet-induced obesity and diabetes through metabolic endotoxemia which triggers the inflammatory tone. Based on recent research, several physiopathological mechanisms involved in the development of obesity are reviewed.

PMID: 19856250

Obese People Have 'Severe Brain Degeneration https://www.livescience.com/10582-obese-people-severe-brain-degeneration.html

Distinct Hypothalamic Neurons Mediate Estrogenic Effects on Energy Homeostasis and ReproductionYong Xu1, 2, 5, Thekkethil P. Nedungadi3, 5, Liangru Zhu1, Nasim Sobhani3, Boman G. Irani3, Kathryn E. Davis3, Xiaorui Zhang1, Fang Zou1, Lana M. Gent3, Lisa D. Hahner3, Sohaib A. Khan4, Carol F. Elias2, Joel K. Elmquist2, Deborah J. Clegg3, ,

1 Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA 2 Division of Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 3 Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA 4 Department of Cancer and Cell Biology, Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA Received 4 November 2010; revised 24 June 2011; Accepted 2 August 2011. Published: October 4, 2011. Available online 4 October 2011.

Referred to by: Estrogens and Obesity: Is It All in Our Heads? Cell Metabolism, Volume 14, Issue 4, 5 October 2011, Pages 435-436, Sarah Hart-Unger, Kenneth S. Korach PDF (164 K) | Summary Estrogens regulate body weight and reproduction primarily through actions on estrogen receptor-α (ERα). However, ERα-expressing cells mediating these effects are not identified. We demonstrate that brain-specific deletion of ERα in female mice causes abdominal obesity stemming from both hyperphagia and hypometabolism. Hypometabolism and abdominal obesity, but not hyperphagia, are recapitulated in female mice lacking ERα in hypothalamic steroidogenic factor-1 (SF1) neurons. In contrast, deletion of ERα in hypothalamic pro-opiomelanocortin (POMC) neurons leads to hyperphagia, without directly influencing energy expenditure or fat distribution. Further, simultaneous deletion of ERα from both SF1 and POMC neurons causes hypometabolism, hyperphagia, and increased visceral adiposity. Additionally, female mice lacking ERα in SF1 neurons develop anovulation and infertility, while POMC-specific deletion of ERα inhibits negative feedback regulation of estrogens and impairs fertility in females. These results indicate that estrogens act on distinct hypothalamic ERα neurons to regulate different aspects of energy homeostasis and reproduction.

Fascinating stuff - especially as we know the Estrogen receptors are downregulated by EBV (and other) species of the microbiota. Obesity a disease? Surely not… :)

..Trevor..

From: Ragnar Michal Schjølberg god_is_wide@hotmail.com To: Trevor Marshall trevor@trevormarshall.com Subject: This Is Your Brain On Estrogen Date: Wed, 5 Oct 2011 13:42:53 +0200 Importance: Normal X-OriginalArrivalTime: 05 Oct 2011 11:42:53.0219 (UTC) FILETIME=[EAD40730:01CC8353]

https://www.sciencedaily.com/releases/2011/10/111004123600.htm

metabolic syndrome

Microbiol Immunol. 2010 Dec;54(12):747-9. doi: 10.1111/j.1348-0421.2010.00281.x. IgA antibodies to Chlamydia trachomatis and metabolic syndrome.

Sehnem L, Bodanese LC, Repetto G, Staub HL.

Department of Nursing and Dentistry, University of Santa Cruz do Sul, Brazil. lucielesehnem@unisc.br

Abstract

Chlamydia pneumoniae may trigger atherogenesis. Chlamydia trachomatis (CT) can also induce endothelial activation. However, its role in metabolic syndrome (METS), a proatherogenic entity, has remained unexplored. In this study the frequencies of IgA and IgG anti-CT antibodies were evaluated by immunoenzymatic assay in METS patients and healthy controls. The survey included 238 individuals (148 with METS). The mean age was 59.7 years. IgA anti-CT antibodies were found significantly more frequently in METS patients (16.9%) than in controls (5.6%) (P= 0.015). The role of such IgA response in METS should be further investigated.

© 2010 The Societies and Blackwell Publishing Asia Pty Ltd. PMID: 21223362

The obesity results from Jeff Gordon at Washington U in mice did not transfer to man. Other groups have shown no link in man between gut species and obesity, even though it was clear in mice. When microbiota is involved, murine studies appear to be worthless.

..Trevor..

The term “infectobesity” refers to obesity of infectious origin and the emerging field of medical research that studies the relationship between pathogens (disease-causing organisms, such as viruses and bacteria) and weight gain. The term was coined in 2001 by Dr. Nikhil V. Dhurandhar, at the Pennington Biomedical Research Center. (Dhurandhar, 2001).

Obes Rev. 2012 Sep;13(9):799-809. doi: 10.1111/j.1467-789X.2012.01009.x. Epub 2012 Jun 11. Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host-microbe interactions contributing to obesity. Payne AN, Chassard C, Lacroix C. Source Institute of Food, Nutrition and Health, ETH Zurich, Zurich, Switzerland. Abstract The Western diet, comprised of highly refined carbohydrates and fat but reduced complex plant polysaccharides, has been attributed to the prevalence of obesity. A concomitant rise in the consumption of fructose and sugar substitutes such as sugar alcohols, artificial sweeteners, even rare sugars, has mirrored this trend, as both probable contributor and solution to the epidemic. Acknowledgement of the gut microbiota as a factor involved in obesity has sparked much controversy as to the cause and consequence of this relationship. Dietary intakes are a known modulator of gut microbial phylogeny and metabolic activity, frequently exploited to stimulate beneficial bacteria, promoting health benefits. Comparably little research exists on the impact of 'unconscious' dietary modulation on the resident commensal community mediated by increased fructose and sugar substitute consumption. This review highlights mechanisms of potential host and gut microbial fructose and sugar substitute metabolism. Evidence is presented suggesting these sugar compounds, particularly fructose, condition the microbiota, resulting in acquisition of a westernized microbiome with altered metabolic capacity. Disturbances in host-microbe interactions resulting from fructose consumption are also explored.

© 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

PMID: 22686435

Sugary Drinks Increase Bad Bacteria in Gut, Risk of Diabetes

submitted by Garth Hogan on September 03, 2012 Tags: bacteria, biome, diabetes, gut, microbiome, obesity, sugar Source: www.medicaldaily.com Sugary drinks help bad microbes grow in the human gut, according to a study published in the journal Obesity Reviews. This increase leads to many health complications like obesity and metabolic syndrome, raising risk of diseases associated with metabolic syndrome like diabetes.

The study says western diet containing sugars, especially fructose, nudge the growth of “westernized microbiome” and this has significant effect on how the food is digested in the gut. Also, presence of these microbes in the gut increases immune response that leads to inflammation.

Earlier research has shown that poor quality diet increases the number of bad bacteria in the gut. This, apart from a weakened immune system (due to low nutrition) starts targeting the body causing inflammation, and subsequent death.

In the study, authors Amanda N. Payne, Ph.D., of the Institute of Food, Nutrition, and Health in Zurich, and colleagues suggest that “obesity treatment and prevention could be effectively achieved by promoting intestinal homeostasis through reintroduction of a balanced and diverse diet,” HealthDay reports.

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