Treating Obesity Seriously Starts By Understanding The Problem
That there are no easy solutions to obesity and managing your weight is challenging at the best of times. But trying to find manage it without understanding even the basics of how your body works to defend its weight is hopeless at best. A sort paper by Christopher Ochner and colleagues, published in The Lancet Diabetes and Endocrinology, succinctly describes the challenges, and appeals to clinicians (and decision makers) to take this problem seriously (instead of trivialising it as a simple “lifestyle” issue). “Many clinicians are not adequately aware of the reasons that individuals with obesity struggle to achieve and maintain weight loss, and this poor awareness precludes the provision of effective intervention.” As readers of these pages are well aware, “Irrespective of starting weight, caloric restriction triggers several biological adaptations designed to prevent starvation. These adaptations might be potent enough to undermine the long-term effectiveness of lifestyle modification in most individuals with obesity, particularly in an environment that promotes energy overconsumption.” But is is not just about the body’s defense mechanisms. “Additional biological adaptations occur with the development of obesity and these function to preserve, or even increase, an individual’s highest sustained lifetime bodyweight. For example, preadipocyte proliferation occurs, increasing fat storage capacity. In addition, habituation to rewarding neural dopamine signalling develops with the chronic overconsumption of palatable foods, leading to a perceived reward deficit and compensatory increases in consumption.” “…improved lifestyle choices might be sufficient for lasting reductions in bodyweight prior to sustained obesity. Once obesity is established, however, bodyweight seems to become biologically stamped in and defended. Therefore, the mere recommendation to avoid calorically dense foods might be no more effective for the typical patient seeking weight reduction than would be a recommendation to avoid sharp objects for someone bleeding profusely.” As the authors point out, “…there is now good evident that these biological adaptations often persist indefinitely, even when a person re-attains a healthy BMI via behaviourally induced weight loss….Thus, we suggest that few individuals ever truly recover from obesity; individuals who formerly had obesity but are able to re-attain a healthy bodyweight via diet and exercise still have ‘obesity in remission’ and are biologically very different from individuals of the same age, sex, and bodyweight who never had obesity.” To overcome these biological adaptations it is not enough to appeal or rely on will-power alone to sustain long-term weight loss. Rather, treatments need to address… Read More »
Early Bird Registration For Canadian Obesity Summit Ends March 3rd
For all my Canadian readers (and any international readers planning to attend), here just a quick reminder that the deadline for early bird discount registration for the upcoming 4th Canadian Obesity Summit in Toronto, April 28 – May 2, ends March 3rd. To anyone who has been at a previous Canadian Summit, attending is certainly a “no-brainer” – for anyone, who hasn’t been, check out these workshops that are only part of the 5-day scientific program – there are also countless plenary sessions and poster presentations – check out the full program here. Workshops: Public Engagement Workshop (By Invitation Only) Pre-Summit Prep Course – Overview of Obesity Management ($50) Achieving Patient‐Centeredness in Obesity Management within Primary Care Settings Obesity in young people with physical disabilities CON-SNP Leadership Workshop: Strengthening CON-SNP from the ground up (Invitation only) Exploring the Interactions Between Physical Well-Being and Obesity Healthy Food Retail: Local public‐private partnerships to improve availability of healthy food in retail settings How Can I Prepare My Patient for Bariatric Surgery? Practical tips from orientation to operating room Intergenerational Determinants of Obesity: From programming to parenting Neighbourhood Walkability and its Relationship with Walking: Does measurement matter? The EPODE Canadian Obesity Forum: Game Changer Achieving and Maintaining Healthy Weight with Every Step Adolescent Bariatric Surgery – Now or Later? Teen and provider perspectives Preventive Care 2020: A workshop to design the ideal experience to engage patients with obesity in preventive healthcare Promoting Healthy Maternal Weights in Pregnancy and Postpartum Rewriting the Script on Weight Management: Interprofessional workshop SciCom-muniCON: Science Communication-Sharing and exchanging knowledge from a variety of vantage points The Canadian Task Force on Preventive Health Care’s guidelines on obesity prevention and management in adults and children in primary care Paediatric Obesity Treatment Workshop (Invitation only) Balanced View: Addressing weight bias and stigma in healthcare Drugs, Drinking and Disordered Eating: Managing challenging cases in bariatric surgery From Mindless to Mindful Waiting: Tools to help the bariatric patient succeed Getting Down to Basics in Designing Effective Programs to Promote Health and Weight Loss Improving Body Image in Our Patients: A key component of weight management Meal Replacements in Obesity Management: A psychosocial and behavioural intervention and/or weight loss tool Type 2 Diabetes in Children and Adolescents: A translational view Weight Bias: What do we know and where can we go from here? Energy Balance in the Weight- Reduced Obese Individual: A biological reality that favours… Read More »
Anti-Inflammatory Effects Of A Healthy Nordic Diet
During my current visit to speak at the Icelandic Medical Association Annual Conference and meet with policy makers, my hosts are doing a wonderful job of introducing me to their “Nordic” fare consisting largely of fish, rye bread and other local produce. Reason enough to post on this recent article by Marjukka Kolehmainen and her team of Scandinavian colleagues, published in the American Journal of Clinical Nutrition, which examines the effects of a Nordic diet on the expression of inflammatory markers in adipose tissue of individuals with the metabolic syndrome. Participants in this 18-24 week study were randomised to either a Nordic or control diet in the SYSDIET study, whereby participants for this “substudy” were selected from centres in Kuopio, Lund and Oulo. Importantly, subjects chosen for this analysis were relatively weight stable, having lost or gained less than 5% of their body weight during the course of the study. In accordance with recommendations for a healthy Nordic diet, subjects in the intervention group were counselled to increase their consumption of whole-grain products, berries, fruits and vegetables, rapeseed oil, have three fish meals per week, and chose low-fat dairy products, while avoiding sugar-sweetened products. In contrast, the control group was advised to consume low-fiber cereal products and dairy fat–based spreads while limiting their fish intake to that generally consumed by the average Nordic population. Gene expression studies were performed in biopsies from subcutaneous fat tissue and showed differential expression of about 130 genes between the two dietary groups – most of which were related to pathways involved in immune and inflammatory response, including genes involved in leukocyte trafficking and macrophage recruitment (e.g., interferon regulatory factor 1, CD97), adaptive immune response (interleukin32, interleukin 6 receptor), and reactive oxygen species (neutrophil cytosolic factor 1). Together, the analyses showed a significant reduction in many of these markers consistent with an “anti-inflammatory” effect of the Nordic diet. As the authors point out, these beneficial effects were seen with very little or no weight loss, suggesting that they are indeed attributable to the changes in dietary intake. These findings may well have implications for us here in Canada, where eating a “Nordic” diet with local ingredients, may well be a far better alternative than trying to emulate a “Mediterranean” diet, the green house impact of which would be anything but healthy. @DrSharma Reykjavik, Iceland
Leptin Mediates Obesity Hypertension – End Of Story!
Some times you think that a scientific question has long been adequately answered when someone comes along and puts any remaining doubts to rest. This happened last week, when Stephanie Simonds and an international group of researchers, in a paper published in Cell, present a rather elegant and sophisticated range of studies clearly demonstrating that the adipocyte-derived hormone leptin is a key mediator of hypertension in diet-induced (and probably other types of) obesity. The reason I thought that this question had already long been put to rest was due to a series of rather convincing animal and human studies published in the early 2000s (some of which I was directly involved in) that nicely demonstrated a) that obesity in hypertension is largely mediated by an increase in (renal) sympathetic activity; b) that leptin stimulates sympathetic activity and sodium retention; c) in dogs and humans leptin concentrations are closely correlated with sympathetic nerve activity and blood pressure. We’ve also known that obese mice lacking leptin or its receptor do not develop hypertension despite considerable weight gain. If anyone should have any remaining questions, these are now answered in the paper by Simonds and colleagues which uses an array of experiments involving animals deficient in leptin or leptin receptors, humans with loss-of-function mutations in leptin and the LepR and show that leptin’s effects on blood pressure are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), an effect that is prevented or reversed by blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH. All of this is interesting and highlights the fact that adipose tissue is far more than a simple storage organ for fat but rather a tissue that plays an active role in the regulation of a wide range of bodily functions. Leptin alone, just one of the many hormones secreted by fat cells (often collectively referred to as adipokines), has been shown to play an important role in appetite and energy regulation, immune function and bone development. As for bringing us a step closer to obesity treatments, the study suggests that it may not be easily possible to harness leptin as a treatment for weight loss, as one expected side effect would be an increase in blood pressure and heart rate – effects that have limited the clinical tolerability of other “sympathomimetic” drugs. @DrSharma Edmonton, AB
Hope For Hypothalamic Obesity And Beyond?
Hypothalamic obesity, is a rare but serious condition that occurs in about 50% of individuals who have suffered injury to their hypothalamus (e.g. because of a craniopharyngoma or trauma). Severe weight gain in these patients may not be all that surprising given that the hypothalamus plays a key role in the regulation of hunger, satiety and other aspects of energy balance. Now, Zafgen, a US biopharmaceutical company, announces surprising early results of treating such patients with beloranib, an inhibitor of methionine aminopeptidase 2 (MetAP2), an enzyme that modulates the activity of key cellular processes that control metabolism. According to Zafgen, their small proof-of-principle trial (ZAF-221), conducted in 14 obese patients (nine women and five men) who were confirmed by magnetic resonance imaging (MRI) to have had hypothalamic injury, the results look most promising. Here is the description of their findings taken from their press release: “ZAF-221 was a randomized, double-blind, placebo controlled study of twice-weekly subcutaneous injections of 1.8 mg beloranib or placebo in patients with HIAO to evaluate weight reduction and safety over four weeks, followed by an optional four week open-label extension. Beloranib treatment resulted in mean weight loss of 3.4 kg and 6.2 kg in patients with HIAO after four and eight weeks of treatment with beloranib, respectively, in contrast to 0.3 kg mean weight loss in patients treated with placebo for four weeks (p = 0.01). Improvements in cardiovascular disease risk factors of lipids and inflammation (measured by C-reactive protein) were also observed. Beloranib 1.8 mg was well tolerated in this population, with no serious or severe adverse events reported. Safety measures such as laboratory, electrocardiogram, and vital sign measurements revealed no signals of concern, and all subjects randomized to beloranib completed the trial.” What I find most surprising about these findings, is that this drug appears to work in people where key centres for appetite regulation are no longer intact. This points to the existence of a non-hypothalamic mode of action for this drug – an action that is powerful enough to work independently of the centres in the brain known to play a key role in energy regulation. The company is also pursuing beloranib for individuals with Prader-Willi Syndrome, another hypothalamic form of obesity as well as patients with severe obesity. Needless to say, this finding may well also hold promise for other forms of obesity, reason enough to closely watch the further development of this compound. @DrSharma Edmonton, AB Disclaimer: I… Read More »
Watch Dr. Sharma in the News!
Listen to Dr. Sharma!
