With all of the recent interest in the gut microbiota as a mediator of systemic inflammation and metabolic disease, it was only a matter of time before researchers would begin targeting pro-inflammatory pathways in the gut to change metabolism.
A proof-of-principle, that this is indeed possible, is presented by Helen Luck and colleagues from the University of Toronto in a paper published in Cell Metabolism.
Using mice models, the researchers not only show that a high-fat diet can alter the gut immune system but also that the chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations is reduced in genetically altered mice that lack beta7 integrin-deficient mice (Beta7null), a driver of gut inflammatory response.
Further more, treatment of high-fat-fed normal mice with the local gut anti-inflammatory agent 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters including insulin resistance (although it had no effect on body weight).
These beneficial effects are are associated with reduced gut permeability and endotoxemia as well as decreased visceral adipose tissue inflammation.
Moreover, treatment with ASA also improved antigen-specific tolerance to luminal antigens.
Thus, as the authors conclude,
“…the mucosal immune system affects multiple pathways associated with systemic insulin resistance and represents a novel therapeutic target in this disease.”
Clearly gut inflammation both in relationship to gut microbiota as well as response to dietary factors is likely to be a hot topic in obesity and metabolic research for the foreseeable future.
Now a study by Benoit Chassaing and colleagues published in NATURE, suggests that dietary emulsifiers may promote weight gain and the metabolic syndrome by altering the composition of intestinal microbes.
The researchers hypothesized that emulsifiers may increase bacterial translocation across intestinal mucosa, thereby promoting local and systemic inflammation as well as affecting the composition of gut bacteria.
Their study in mice show that relatively low concentrations of two commonly used emulsifiers (carboxymethylcellulose and polysorbate-80) can induce low-grade systemic inflammation, weight gain and features of the metabolic syndrome, as well as promote intestinal inflammation in mice susceptible to inflammatory bowel disease.
Importantly, they used germ-free mice and faecal transplants to show that these changes can be induced simply by transferring the gut microbes from emulsifier-treated animals to controls.
As the authors note,
“These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.”
While these findings (if replicated in humans) certainly point to the industrial use of food emulsifiers as a potential cause of the global increase in obesity and inflammatory bowel disease, given that these compounds are present in virtually all processed foods, they may well be difficult to avoid.
Guess it’s back to home cooking with raw ingredients.
The camp is open to a select group of graduate and post-graduate trainees from a wide range of disciplines with an interest in obesity research. Over nine days, the trainees are mentored and have a chance to learn about obesity research in areas ranging from basic science to epidemiology and childhood obesity to health policy.
Now, a formal network analysis of bootcamp attendees, published by Jenny Godley and colleagues in the Journal of Interdisciplinary Healthcare, documents the substantial impact that this camp has on the careers of the trainees.
As the analysis of trainees who attended this camp over its first 5 years of operation (2006-2010) shows, camp attendance had a profound positive impact on their career development, particularly in terms of establishing contacts and professional relationships.
Thus, both the quantitative and the qualitative results demonstrate the importance of interdisciplinary training and relationships for career development in obesity researcher (and possibly beyond).
Personally, participation at this camp has been one of the most rewarding experiences of my career and I look forward to continuing this annual exercise for years to come.
To apply for the 2015 Bootcamp, which is also open to international trainees – click here.
Godley J, Glenn NM, Sharma AM, & Spence JC (2014). Networks of trainees: examining the effects of attending an interdisciplinary research training camp on the careers of new obesity scholars. Journal of multidisciplinary healthcare, 7, 459-70 PMID: 25336965
If you have a professional interest in obesity, it’s your #1 destination for learning, sharing and networking with experts from across Canada around the world.
In 2015, the Canadian Obesity Network (CON-RCO) and the Canadian Association of Bariatric Physicians and Surgeons (CABPS) are combining resources to hold their scientific meetings under one roof.
The 4th Canadian Obesity Summit (#COS2015) will provide the latest information on obesity research, prevention and management to scientists, health care practitioners, policy makers, partner organizations and industry stakeholders working to reduce the social, mental and physical burden of obesity on Canadians.
The COS 2015 program will include plenary presentations, original scientific oral and poster presentations, interactive workshops and a large exhibit hall. Most importantly, COS 2015 will provide ample opportunity for networking and knowledge exchange for anyone with a professional interest in this field.
Abstract submission is now open – click here
- Notification of abstract review: January 8, 2015
- Call for late breaking abstracts open: Jan 12-30, 2015
- Notification of late breaking abstracts and handouts and slides due : Feb 27, 2015
- Early registration deadline: March 3, 2015
For exhibitor and sponsorship information – click here
To join the Canadian Obesity Network – click here
I look forward to seeing you in Toronto next year!
This issue of “healthy obesity” was the topic of the 13th Stock Conference of the International Association of the Study of Obesity, the proceeding of which are now published in Obesity Reviews.
As the authors note,
“The ‘healthy obese’ phenotype was described in the 1980s, but major advancements in its characterization were only made in the past five years. During this time, several new mechanisms that may be involved in health preservation in obesity were proposed through the use of transgenic animal models, use of sophisticated imaging techniques and in vivo measurements of insulin sensitivity. However, the main obstacle in advancing our understanding of the metabolically healthy obese phenotype and its related long-term health risks is the lack of a standardized definition.”
The latter is a real problem because finding people with obesity, who are truly metabolically and otherwise healthy becomes harder the higher the BMI gets – this makes the study of this phenomenon rather challenging.
“One of the most consistent characteristics of metabolic health in obesity across studies in humans is reduced liver lipid. This is likely the consequence of increased capacity for storing fat coupled with improved mitochondrial function in adipose tissue and decreased de novo lipogenesis in liver. This can also result in decreased deposition of lipids, including bioactive species, in skeletal muscle. Decreased adipose tissue inflammation with decreased macrophages and a unique T-cell signature with an anti-inflammatory circulating milieu were also suggested to characterize metabolic health in obesity. Anecdotal data support a possible role for healthier lifestyle, including increased level of physical activity and healthier diet. It remains to be established whether a favourable metagenomic signature is a characteristic of metabolic health in obesity.”
Finland’s, Dr Kirsi Pietiläinen explained that,
“..three energy dissipation pathways, oxidative phosphorylation, fat oxidation and amino acid catabolism showed preserved pathway activities in subjects who are MHO at a level similar to their lean counterparts. In contrast, these pathways were significantly down-regulated in adipose samples from obese twins with metabolic disturbances. Another potential hallmark of metabolic health, a favourable inflammatory profile of the adipose tissue was also observed in the MHO twins. Also, the fat cells of the MHO twins were smaller with evidence of more active differentiation processes within the fat tissue. As multiple mitochondrial pathways are vital in adipocyte differentiation , it is possible that mitochondrial malfunction impairs the development of new fat cells, which in turn results in an inability of the adipose tissue to expand under conditions of energy excess. This failure of fat cell proliferation has long been suspected to constitute the framework for ectopic fat storage, insulin resistance and type 2 diabetes.”
Other speakers discussed other aspects including immune function and microbiata in this phenomenon.
Finally, the authors concluded that,
“identifying underlying factors and mechanisms associated with this phenotype will eventually be invaluable in helping the scientific and medical community understand factors that predispose, delay or protect obese individuals from metabolic disturbances. It is essential to underscore that the MHO concept presently only address the cardio-metabolic risks associated with obesity; it is therefore important that patients who are MHO are still very likely to present many other obesity-related complications such as altered physical and/or physiological functional status, sleep problems, articulation and postural problems, stigma, etc. Importantly, the MHO concept supports the fact that classification based on excess adiposity per se (e.g. BMI or body composition if available) should be supplemented with obesity-related comorbidities, e.g. with fasting insulin as proposed by the Edmonton obesity classification system.”
Certainly a space to watch as we learn more and more about the “healthy obesity” phenotype.
Samocha-Bonet D, Dixit VD, Kahn CR, Leibel RL, Lin X, Nieuwdorp M, Pietiläinen KH, Rabasa-Lhoret R, Roden M, Scherer PE, Klein S, & Ravussin E (2014). Metabolically healthy and unhealthy obese – the 2013 Stock Conference report. Obesity reviews : an official journal of the International Association for the Study of Obesity PMID: 25059108