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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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