Friday, December 5, 2014

Hypothalamic Inflammation In Human Obesity

sharma-obesity-astrogliosisRegular readers may recall the exciting body of work from animal models of obesity showing that hypothalamic inflammation involving microscarring (gliosis) may play an important role in appetite and energy regulation in obesity.

Now, a study by Josep Puig and colleagues from the University of Girona, Spain, published in the Journal of Clinical Endocrinology and Metabolism, provides evidence for a similar process in humans.

The researchers used an MRI technique called diffusion tensor imaging (DTI) to measure hypothalamic damage in 24 consecutive middle-aged obese subjects (average BMI 43) and 20 healthy volunteers (average BMI 24).

Not only did the obese participants show greater signs of hypothalamic inflammation but these changes were also strongly associated with higher BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests.

While these studies do not prove cause and effect, these findings are consistent with findings in animal models and point to the role of pro-inflammatory pathways in the areas of the brain known to be intimately linked to appetite and energy regulation.

Understanding what exactly triggers this inflammatory response (in animal models, one fact appears to be a high-fat diet) and how this process could be inhibited, may open new avenues for obesity prevention and treatment.

@DrSharma
Madrid, Spain

ResearchBlogging.orgPuig J, Blasco G, Daunis-I-Estadella J, Molina X, Xifra G, Ricart W, Pedraza S, Fernández-Aranda F, & Fernández-Real JM (2014). Hypothalamic damage is associated with inflammatory markers and worse cognitive performance in obese subjects. The Journal of clinical endocrinology and metabolism PMID: 25423565

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Thursday, December 4, 2014

Can Gut Bugs Cause Depression?

sharma-obesity-gut-buts1Regular readers will by now be well aware of the rapidly growing body of researcher supporting the idea that your gut bugs (of which you have more than you have cells in your body) may well play a key role in determining your risk for obesity and other metabolic disorders.

Now, a paper by Ruth Ann Luna and Jane Foster from Baylor College of Medicine and McMaster University, respectively, published in Current Opinion in Biotechnology, review the evidence that gut bugs may well also have significant effects on your stress response as well as other aspects of mental healthy, including depression.

As one example, they cite a study that shows,

“…a general underrepresentation of the Bacteroidetes phylum in depressed patients and an association of the Lachnospiraceae family with the depression group, and interestingly, even with a decrease in Bacteroidetes, specific operational taxonomic units (OTUs) identified as members of the Bacteroidetes phylum correlated with depression.”

They also cite a number of studies showing that stress can affect gut bug populations and that certain gut bacteriomes are associated with a greater stress response, suggesting that the relationship between gut bugs and stressors may well be a two-way street.

The authors go on to describe a number of pathways that may link gut bugs to humoral, neural, and cellular signaling pathways to brain function.

Clearly, this appears a rich area of research that may well reveal pathways common to both neurological and metabolic issues, both of which may turn out to be amenable to dietary and probiotic interventions.

@DrSharma
London, UK

ResearchBlogging.orgLuna RA, & Foster JA (2014). Gut brain axis: diet microbiota interactions and implications for modulation of anxiety and depression. Current opinion in biotechnology, 32C, 35-41 PMID: 25448230

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Wednesday, December 3, 2014

Does Your Liver Control Your Appetite?

Fatty Liver

Fatty Liver

The answer may well be “yes”, at least if you happen to be a mouse.

In a rather exciting study by Iliana López-Soldado and colleagues from the Institute for Research in Biomedicine, Barcelona, published in DIABETES, the researchers show that increased liver glycogen content may affect appetite (measured as food intake) and otherwise have beneficial effects on metabolism.

In their experiments, the researchers used genetically modified mice, which overexpress an enzyme (PTG) resulting in increased liver glycogen.

Not only did these animals reduce their food intake when fed a high fat diet, they also did not develop the typical glucose intolerance, elevated insulin levels and fatty liver seen in normal mice on this diet.

Apart from losing weight (associated with lower leptin levels), these animals also had lower expression of neuropeptide Y (NPY) and higher expression of propiomelanocortin (POMC) in the hypothalamus.

Thus, the authors summarize their findings as follows:

:…liver glycogen accumulation caused a reduced food intake, protected against the deleterious effects of a HFD and diminished the metabolic impact of fasting. Therefore, we propose that hepatic glycogen content be considered a potential target for the pharmacological manipulation of diabetes and obesity.”

As a number of compounds exist that may do exactly that, these studies may point to a novel pathway for the pharmacological treatment of obesity – but let’s keep in mind that the road from finding in mice to effective treatments in humans is a long and thorny road.

@DrSharma
Edmonton, AB

ResearchBlogging.orgLópez-Soldado I, Zafra D, Duran J, Adrover A, Calbó J, & Guinovart JJ (2014). Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model. Diabetes PMID: 25277398

 

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Thursday, November 20, 2014

Obesity Myth: Losing Weight Is Always Beneficial For Your Health

sharma-obesity-scale2Another common misconception about obesity discusses in our recent paper in Canadian Family Medicine, is the notion that anyone with excess weight stands to benefit from losing weight.

The benefits of weight loss, however are far from as established as most of us may think:

“The strong biological response to weight loss (even the recommended 5% to 10% of baseline weight) involves comprehensive, persistent, and redundant adaptations in energy homeostasis that underlie the high recidivism rate of obesity treatment.

The multiple systems regulating energy stores and opposing the maintenance of a reduced body weight illustrate that fat stores are actively defended.

Among the adverse effects of weight loss, it is well known that body fat loss increases the drive to eat, reduces energy expenditure to a greater extent than predicted, and increases the tendency toward hypoglycemia.

Weight loss is also related to psychological stress, increased risk of depressive symptoms, and increased levels of persistent organic pollutants that promote hormone disruption and metabolic complications, all of which are adaptations that substantially increase the risk of weight regain.

In addition, there is considerable concern about the negative effect of “failed” weight-loss attempts on self-esteem, body image, and mental health.

Thus, clinicians should document and consider the powerful biological counter-regulatory responses and potential undesired effects of weight loss to maximize the success of their interventions. Obesity is a chronic condition and its management requires realistic and sustainable treatment strategies.

Successful obesity management requires identifying and addressing the obesity drivers as well as the barriers to and potential complications of weight management. Family physicians should discuss the possible adverse effects of weight loss with their patients and actively look for these effects in patients trying to lose weight.”

@DrSharma
Wellington, NZ

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Friday, October 24, 2014

Social Network Analysis of the Obesity Research Boot Camp

bootcamp_pin_finalRegular readers may recall that for the past nine years, I have had the privilege and pleasure of serving as faculty of the Canadian Obesity Network’s annual Obesity Research Summer Bootcamp.

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.

@DrSharma
Toronto, ON

ResearchBlogging.orgGodley 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

 

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In The News

Diabetics in most need of bariatric surgery, university study finds

Oct. 18, 2013 – Ottawa Citizen: "Encouraging more men to consider bariatric surgery is also important, since it's the best treatment and can stop diabetic patients from needing insulin, said Dr. Arya Sharma, chair in obesity research and management at the University of Alberta." Read article

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