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CON Co-Hosts the International Congress on Obesity in Vancouver

As Canada’s national representative in the World Obesity Federation (formerly IASO), the Canadian Obesity Network is proud to co-host the 13th International Congress on Obesity in Vancouver, 1-4 May 2016. The comprehensive scientific program will span 6 topic areas: Track 1: From genes to cells For example: genetics, metagenomics, epigenetics, regulation of mRNA and non–coding RNA, inflammation, lipids, mitochondria and cellular organelles, stem cells, signal transduction, white, brite and brown adipocytes Track 2: From cells to integrative biology For example: neurobiology, appetite and feeding, energy balance, thermogenesis, inflammation and immunity, adipokines, hormones, circadian rhythms, crosstalk, nutrient sensing, signal transduction, tissue plasticity, fetal programming, metabolism, gut microbiome Track 3: Determinants, assessments and consequences For example: assessment and measurement issues, nutrition, physical activity, modifiable risk behaviours, sleep, DoHAD, gut microbiome, Healthy obese, gender differences, biomarkers, body composition, fat distribution, diabetes, cancer, NAFLD, OSA, cardiovascular disease, osteoarthritis, mental health, stigma Track 4: Clinical management For example: diet, exercise, behaviour therapies, psychology, sleep, VLEDs, pharmacotherapy, multidisciplinary therapy, bariatric surgery, new devices, e-technology, biomarkers, cost effectiveness, health services delivery, equity, personalised medicine Track 5: Populations and population health For example: equity, pre natal and early nutrition, epidemiology, inequalities, marketing, workplace, school, role of industry, social determinants, population assessments, regional and ethnic differences, built environment, food environment, economics Track 6: Actions, interventions and policies For example: health promotion, primary prevention, interventions in different settings, health systems and services, e-technology, marketing, economics (pricing, taxation, distribution, subsidy), environmental issues, government actions, stakeholder and industry issues, ethical issues Early-bird registration is now open – click here Abstract submission deadline is November 30, 2015 – click here For more information including sponsorship and exhibiting at ICO 2016 – click here I look forward to welcoming you to Vancouver next year. @DrSharma Toronto, ON  

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Are We More Susceptible to Obesity Than Before?

Regular readers will be familiar with my wariness of epidemiological data on diet and activity – especially, when these are self-reported. Nevertheless, for what it is worth, a publication by Ruth Brown and colleagues from York University, Toronto, published in Obesity Research and Clinical Practice, suggests that people today may be more susceptible to obesity than just a few decades ago. The study looks at self-reported dietary from 36,377 U.S. adults from the National Health and Nutrition Survey (NHANES) between 1971 and 2008 and physical activity frequency data from 14,419 adults between 1988 and 2006 (no activity data was available from earlier years). Between 1971 and 2008, BMI, total caloric intake and carbohydrate intake increased 10-14%, and fat and protein intake decreased 5-9%. Between 1988 and 2006, frequency of leisure time physical activity increased 47-120%. However, for a given amount of caloric intake, macronutrient intake or leisure time physical activity, the predicted BMI was up to 2.3kg/m2 higher in 2006 that in 1988. So unless there was some major systematic shift in what people were reporting (which seems somewhat unlikely) it is clear that factors other than diet and physical activity may be contributing to the increase in BMI over time – or in other words, it appears that people today, for the same caloric intake and physical activity, are more likely to have a higher BMI than people living a few decades ago. There are of course several plausible biological explanations for these findings including epigenetics, obesogenic environmental toxins, alterations in gut microbiota to name a few. If nothing else, these data support the notion that there is more to the obesity epidemic than just eating too much and not moving enough. @DrSharma Edmonton, AB

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How the FTO Gene Contributes to Obesity

While I took a month off from blogging, an international group of researchers published what may well become a landmark paper on the genetics of obesity in the New England Journal of Medicine. As regular readers may be well aware, a number of previous genetic studies have pointed to the importance of the FTO gene for human obesity – however, what exactly this gene does to effect body weight was largely unclear. The rs1421085 single-nucleotide variant of this gene has both a high frequency and a strong effect size, which suggests positive selection or bottlenecks (e.g., 44% frequency in European populations vs. 5% in African populations). In the present paper, that included examination of epigenomic data, allelic activity, motif conservation, regulator expression, and gene coexpression patterns in mice and humans, the researchers showed that the FTO allele associated with obesity represses mitochondrial energy production in adipocyte precursor cells in a tissue-autonomous manner. To be precise, the rs1421085 variant of this gene apparently disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation. These molecules play key roles in thermogenic dissipation both through UCP-1 and UCP-1-independent pathways. This change leads to a persistent and cell-autonomous developmental shift from energy-dissipating beige (brite) adipocytes to energy-storing white adipocytes, with a reduction in mitochondrial thermogenesis by a factor of 5. It is also associated with an increase in lipid storage and adipocyte cell size. Inhibition of Irx3 in adipose tissue in mice reduced body weight and increased energy dissipation without a change in physical activity or appetite. Knockdown of IRX3 or IRX5 in primary adipocytes from human subjects with the risk allele restored thermogenesis, increasing it by a factor of 7, and overexpression of these genes had the opposite effect in adipocytes from nonrisk-allele carriers.   Finally, repair of the ARID5B motif in primary cultured adipocytes from a patient with the risk allele restored IRX3 and IRX5 repression, activated browning expression programs, and restored thermogenesis, increasing it by a factor of 7. These deep insights into the function of what is apparently a key pathway in human susceptibility (or resistance) to obesity, offers a number of potential targets for pharmacological interventions for obesity – something that we desperately need for patients struggling with this issue. However, as an accompanying editorial is quick to point out, “As yet, there… Read More »

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Limbic Effects On Physical Activity And Obesity

The amygdala is a part of the so-called limbic system that performs a primary role in the processing of memory, decision-making, and emotional reactions. The amygdala has also been implicated in a variety of mental health problems including anxiety, binge drinking and post-traumatic stress syndrome. A study by Xu and colleagues, published in the Journal of Clinical Investigation now shows that in mice, activity of the estrogen receptor–α (ERα) in the medial amygdala may have a profound influence on the development of obesity – an effect, which appears to me largely mediated through effects on physical activity. Building on previous work showing that ERα activity in the brain prevents obesity in both males and female rats, the researchers used a series of complex experiments to demonstrate that specific deletion of the ERα gene from SIM1 neurons, which are highly expressed in the medial amygdala, cause a marked decrease in physical activity and weight gain in both male and female mice fed with regular chow, without any increase in food intake. In addition, this deletion caused increased susceptibility to diet-induced obesity in males but not in females. Deletion of the ERα receptor also blunted the body weight-lowering effects of a glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate. In contrast, over-expression or stimulation of SIM1 neurons increased physical activity in mice and protected them from diet-induced obesity. These findings point to a novel mechanism of neuronal control of physical activity, which in turn appears to have important effects on the susceptibility to weight gain. @DrSharma Edmonton, AB

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Transgenerational Transmission of Metabolic Disease

If  anyone ever tells you that the current obesity epidemic can have nothing to do with genetics because “genes don’t change in a couple of generations”, it is completely fair to let them know that they probably do not know what they are talking about. Indeed, there is now overwhelming evidence showing that a variety of health problems, particularly related to metabolic diseases including obesity, can well be transmitted from generation to generation as a result of epigenetic modifications that persist in subsequent generations, even if these are no longer exposed to the “trigger” environment. Anyone who is interested in learning about how much we know about these intergenerational mechanisms, will probably want to read a recent review article on this subject by Rachel Stegemann and David Buchner, published in Seminars in Cell & Developmental Biology. In this papers the authors review examples of transgenerational inheritance of metabolic disease in both humans and model organisms and how these can be triggered by both genetic and environmental stimuli.ors As the authors note, “A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation.” They also discuss example of therapeutically targeting the epigenome (e.g. through dietary modification or exercise) to prevent the transgenerational transmission of metabolic disease. These findings have substantial implications for our attempts to prevent or even reverse the development of obesity in future generations. @DrSharma Vancouver, BC

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