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The Key To Obesity Management Lies In The Science Of Energy Homeostasis

If there is one thing we know for sure about obesity management, it is the sad fact, that no diet, exercise, medication, not even bariatric surgery, will permanently reset the body’s tendency to defend and regain its body weight to its set point – this generally being the highest weight that has been achieved and maintained for a notable length of time.

Thus, any effective long-term treatment has to offset the complex neurobiology that will eventually doom every weight-loss attempt to “failure” (no, anecdotes don’t count!).

Just how complex and overpowering this biological system that regulates body weight is, is described in a comprehensive review by the undisputed leaders in this field (Michael Schwartz, Randy Seeley, Eric Ravussin, Rudolph Leibel and colleagues) published in Endocrine Reviews. Indeed the paper is nothing less than a “Scientific Statement” from the venerable Endocrine Society, or, in other words, these folks know what they’re talking about when it comes to the science of energy balance.

As the authors remind us,

“In its third year of existence, the Endocrine Society elected Sir Harvey Cushing as President. In his presidential address, he advocated strongly in favor of adopting the scientific method and abandoning empiricism to better inform the diagnosis and treatment of endocrine disease. In doing so, Cushing helped to usher in the modern era of endocrinology and with it, the end of organo-therapy. (In an interesting historical footnote, Cushing’s Energy Homeostasis and the Physiological Control of Body-Fat Stores presidential address was given in , the same year that insulin was discovered.)”

Over 30 pages, backed by almost 350 scientific citations, the authors outline in excruciating detail just how complex the biological system that regulates, defends, and restores body weight actually is. Moreover, this system is not static but rather, is strongly influenced and modulated by environmental and societal factors.

Indeed, after reading this article, it seems that the very notion, that average Jane or Joe could somehow learn to permanently overcome this intricately fine-tuned system (or the societal drivers) with will power alone is almost laughable (hats off to the very few brave and determined individuals, who can actually do this – you have climbed to the top of Mount Everest and decided to camp out there for the foreseeable future – I wish you all the best!).

Thus, the authors are confident that,

“The identification of neuromolecular mechanisms that integrate short-term and long-term control of feeding behavior, such that calorie intake precisely matches energy expenditure over long time intervals, will almost certainly enable better preventive and therapeutic approaches to obesity.”

Sadly, despite all we have learnt about this system, we are still far from fully understanding it. Thus, the canonical molecular/ cellular signaling pathway: LEP → LEPR → POMC, AgRP → PC → MC4R is just one pathway in a complex network of multiple interacting and sometimes redundant pathways that involve virtually every part of the brain.

Also, the effect of environmental factors appears to be far more complex than most people think. Thus,

“During sensitive periods of development, ontogenic processes in both brain and peripheral organs can be modified so as to match anticipated environmental conditions. Although many exposures during development could potentially predispose to obesity in adulthood, we focus here on two that some researchers think contribute to the secular trends in obesity: parental obesity and exposure to endocrine disrupting chemicals (EDCs).”

Throw in the role of gut bugs, infections, and societal factors, and it is easy to see why no simple solution to the obesity epidemic are in sight (let alone a range of effective long-term treatments like we have for most other common chronic diseases).

As for solutions,

“To be viable, theories of obesity pathogenesis must account not only for how excess body fat is acquired, but also for how excess body fat comes to be biologically defended. To date, the preponderance of research has focused on the former. However, we must consider the possibility that some (perhaps even most) mechanisms underlying weight gain are distinct from those responsible for the biological defense of excess fat mass. A key question, therefore, is how the energy homeostasis system comes to defend an elevated level of fat mass (analogous to the defense of elevated blood pressure in patients with hypertension). Answering this question requires an improved understanding of the neuro-molecular elements that underlie a “defended” level of body fat. What are the molecular/neuroanatomic predicates that help establish and defend a “set point” for adiposity? How do these elements regulate feeding behavior and/or energy expenditure, so as to achieve long-term energy balance? By what mechanisms is an apparently higher set point established and defended in individuals who are obese?” [sic]

Clearly,

“Given that recovery of lost weight (the normal, physiological response to weight loss irrespective of one’s starting weight) is the largest single obstacle to effective long-term weight loss, we cannot overstate the importance of a coherent understanding of obesity-associated alterations of the energy homeostasis system.”

There is much work to be done. Whether or not, in this climate of anti- and pseudo-science, funding for such fundamental work will actually be made available, is anyone’s guess.

@DrSharma
Edmonton, AB

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Alternate Day Fasting Is No Better Than Any Other Fad Diet

It seems that every year someone else comes up with a diet that can supposedly conquer obesity and all others health problems of civilization.

In almost every case, the diet is based on some “new” insight into how our bodies function, or how our ancestors (read – hunters gatherers (never mind that they only lived to be 35) ate, or how modern foods are killing us (never mind that the average person has never lived longer than ever before), or how (insert remote population here) lives today with no chronic disease.

Throw in some scientific terms like “ketogenic”, “guten”, “anti-oxidant”, “fructose”, or “insulin”, add some level of restriction and unusual foods, and (most importantly) get celebrity endorsement and “testemonials” and you have a best-seller (and a successful speaking career) ready to go.

The problem is that, no matter what the “scientific” (sounding) theories suggest, there is little evidence that the enthusiastic promises of any of these hold up under the cold light of scientific study.

Therefore, I am not the least surprised that the same holds true for the much hyped “alternative-day fasting diet”, which supposedly is best for us, because it mimics how our pre-historic ancestors apparently made it to the ripe age of 35 without obesity and heart attacks.

Thus, a year-long randomised controlled study by John Trepanowski and colleagues, published in JAMA Internal Medicine, shows that alternate day fasting is evidently no better in producing superior adherence, weight loss, weight maintenance, or cardioprotection compared to good old daily calorie restriction (which also produces modest long-term results at best).

In fact, the alternate day fasting group had significantly more dropouts than both the daily calorie restriction and control group (38% vs. 29% and 26% respectively). Mean weight loss was virtually identical between both intervention groups (~6 Kg).

Purists of course will instantly critisize that the study did not actually test alternative-day fasting, as more people dropped out and most of the participants who stayed in that group actually ate more than prescribed on fast days, and less than prescribed on feast days – but that is exactly the point of this kind of study – to test whether the proposed diet works in “real life”, because no one in “real life” can ever be expected to be perfectly compliant with any diet. In fact, again, as this study shows, the more “restrictive” the diet (and, yes, starving yourself every other day is “restrictive”), the greater the dropout rate.

Unfortunately, what counts in real life is not what people should be doing, but what people actually do. The question really is not whether or not alternate-day fasting is better for someone trying to lose weight but rather, whether or not “recommending” someone follows an alternate-day fasting plan (and them trying to follow it the best they can) is better for them. The clear answer from this study is “no”.

So why are all diets the same (in that virtually all of them provide a rather modest degree of long-term weight loss)?

My guess is that no diet (or behaviour for that matter) has the capability of fundamentally changing the body’s biology that acts to protect and restore body fat in the long-term. Irrespective of whether a diet leads to weight loss in the short term and irrespective of how it does so (or how slow or fast), ultimately no diet manages to “reset” the body-weight set point to a lower level, that would biologically “stabilize” weight loss in the long-term.

Thus, the amount of long-term weight loss that can be achieved by dieting is always in the same (rather modest) ballpark and it is often only a matter of time before the biology wins out and put all the weight back on.

Clearly, I am not holding my breath for the next diet that comes along that promises to be better than everything we’ve had before.

My advice to patients is, do what works for you, but do not expect miracles – just find the diet you can happily live on and stick to it.

@DrSharma
Edmonton, AB

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Zona Incerta Stimulation Provokes Instant Binge Eating in Mice

The neuronal control of appetite and food intake is among the most complex and fascinating systems.

Now, in a paper published in Science, Xiaobing Zhang and Anthony van den Pol from Yale University, New Haven, report the identification of a novel role of the zona incerta in inducing profound binge eating behaviour in mice.

The zona incerta, is a little know part of the central nervous system within the subthalamus with extensive projections all the way from the cerebral cortex into the spinal cord. It is thought to play an important role in limbic-motor integration as well as synchronizing brain rhythms.

The researchers showed that optogenetic stimulation of zona incerta GABA neurons or their axonal projections to paraventricular thalamus excitatory neurons rsults in an immediate (in 2 to 3 seconds) binge-like eating behaviour – the animals ate up to 35% of their total energy requirements in just 10 mins.

Furthermore, while intermittent stimulation of these neurons led to body weight gain, ablation reduced weight.

The authors suggest that the identification of this novel orexigenic system may lead to better treatments not just for binge-eating disorder.

@DrSharma
Edmonton, AB

 

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Preventing and Managing Childhood Obesity

This morning, I am presenting a plenary talk in Berlin to about 200 colleagues involved in childhood obesity prevention.

The 1-day symposium is hosted by Plattform Ernährung und Bewegung  e.V. (Platform for Nutrition and Physical Activity), a German consortium of health professionals as well as public and private stakeholders in public health.

Although, as readers are well aware, I am by no means an expert on childhood obesity, I do believe that what we have learnt about the complex socio-psycho-biology of adult obesity in many ways has important relevance for the prevention and management of childhood obesity.

Not only do important biological factors (e.g. genetics and epigenetics) act on the infant, but, infants and young children are exposed to the very same societal, emotional, and biological factors that promote and sustain adult obesity.

Thus, children do not grow up in isolation from their parents (or the adult environment), nor do other biological rules apply to their physiology.

It should thus be obvious, that any approach focussing on children without impacting or changing the adult environment will have little impact on over all obesity.

This has now been well appreciated in the management of childhood obesity, where most programs now take a “whole-family” approach to addressing the determinants of excess weight gain. In fact, some programs go as far as to focus exclusively on helping parents manage their own weights in the expectation (and there is some data to support this) that this will be the most effective way to prevent obesity in their offspring.

As important as the focus on childhood obesity may be, I would be amiss in not reminding the audience that the overwhelming proportion of adults living with obesity, were normal weight (even skinny!) kids and did not begin gaining excess weight till much later in life. Thus, even if we were somehow (magically?) to completely prevent and abolish childhood obesity, it is not at all clear that this would have a significant impact on reducing the number of adults living with obesity, at least not in the foreseeable future.

Let us also remember that treating childhood obesity is by no means any easier than managing obesity in adults – indeed, one may argue that effectively treating obesity in kids may be even more difficult, given the the most effective tools to managing this chronic disease (e.g. medications, surgery) are not available to those of us involved in pediatric obesity management.

Thus, I certainly do not envy my pediatric colleagues in their struggles to provide meaningful obesity management to their young clients.

I am not sure how my somewhat sobering talk will be received by this public health audience, but then again, I don’t think I was expected to fully toe the line when it comes to exclusively focussing on nutrition and activity (as important as these factors may be) as an effective way to prevent or even manage childhood obesity.

@DrSharma
Berlin, D

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Another Canadian Obesity Summit Exceeds Expectations

Wow, what a week!

Just back from the 5th Canadian Obesity Summit, there is no doubt that this summit will live long in the minds (and hearts) of the over 500 attendees from across Canada and beyond.

As anyone would have appreciated, the future of obesity research, prevention and practice is alive and kicking in Canada. The over 50 plenary review lectures as well as the over 200 original presentations spanning basic cellular and animal research to health policy and obesity management displayed the gamut and extent of cutting-edge obesity research in Canada.

But, the conference also saw the release of the 2017 Report Card on Access to Obesity Treatment for Adults, which paints a dire picture of treatment access for the over 6,000,000 Canadians living with this chronic disease. The Report Card highlights the virtually non-existant access to multidisciplinary obesity care, medically supervised diets, or prescription drugs for the vast majority of Canadians.

Moreover, the Report Card reveals the shocking inequalities in access to bariatric surgery between provinces. Merely crossing the border from Alberta to Saskatchewan and your chances of bariatric surgery drops from 1 in 300 to 1 in 800 per year (for eligible patients). Sadly, numbers in both provinces are a far cry from access in Quebec (1 in 90), the only province to not get an F in the access to bariatric surgery category.

The presence of patient champions representing the Canadian Obesity Network’s Public Engagement Committee, who bravely told their stories to a spell-bound audience (often moved to tears) at the beginning of each plenary session provided a wake up call to all involved that we are talking about the real lives of real people, who are as deserving of respectful and effective medical care for their chronic disease as Canadians living with any other chronic disease.

Indeed, the clear and virtually unanimous acceptance of obesity as a chronic medical disease at the Summit likely bodes well for Canadians, who can now perhaps hope for better access to obesity care in the foreseeable future.

Thanks again to the Canadian Obesity Network for hosting such a spectacular event (in spectacular settings).

More on some of the topics discussed at the Summit in coming posts.

For an overview of the Summit Program click here

@DrSharma
Edmonton, AB

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