Study: A Setback for the 'Obesity Vaccine'

By Lindsay Abrams

Knocking out a hunger hormone called ghrelin is known to decrease appetite and food intake -- but it also leads to a more anxiety-ridden response to stress.

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PROBLEM: Levels of ghrelin, a hormone in the stomach, rise and fall with hunger -- an observation which has lead scientists to explore ghrelin repression as a possible method of combating obesity. In fact, an "obesity vaccine" that decreases ghrelin has already been shown to both decrease food intake and increase energy expenditure in animals (but while two major studies have attested to its feasibility, it has yet to be injected into humans). 

Ghrelin is also involved in the response to stress, but previous studies have not been able to agree on its exact role. We do know, however, that increased stress often drives people toward increased, high-fat food consumption, and is recognized as a contributing factor to weight gain. Understanding the consequences of reduced ghrelin -- whether it would result in increased or decreased anxiety -- would therefore have direct implications for the "obesity vaccine" as a viable treatment.


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METHODOLOGY: Mice who had been genetically modified to lack ghrelin receptors were put through a variety of behavioral tests through which researchers could interpret their anxiety levels. Then, after getting the mice good and stressed out, the researchers repeated these tests to measure their response. Their anxiety levels were compared to those of normal, ghrelin-controlled mice. The researchers also study the mice's brains, hormone levels, and gene expression as alternative ways of understanding their physiological response to stress.

RESULTS: When they weren't exposed to stressful conditions, mice without ghrelin receptors were significantly less anxious than the normal mice. But under acute stress, their anxiety levels went into overdrive. The normal mice, on the other hand, responded to stress with both the release of ghrelin and comparatively lower levels of anxiety.

CONCLUSION: It turns out that ghrelin's role in stress response is context specific: it increases anxiety in calm environments but reduces it in stressful situations. The authors note that this is the first study to show that ghrelin "prevents a hyperactive, over-anxious response to acute stress." So the reduced appetite caused by ghrelin suppression might come at the cost of increased anxiety.

IMPLICATIONS: Aside from being unpleasant, we of course know that chronic stress is in many ways bad your health. The authors point out that an evolutionary response to stress is to eat more, hypothesizing that "under conditions of acute stress, ghrelin limits excessive anxious behavior by promoting the feeling of reward to ensure appropriate food-seeking behavior and maintain energy homeostasis." With enough stress, compensatory eating could end up counteracting the vaccine's effects, leaving us right back where we started.

The full study, "Ghrelin regulates the hypothalamic-pituitary-adrenal axis and restricts anxiety after acute stress," is published in the journal Biological Psychiatry .

This article available online at:

http://www.theatlantic.com/health/archive/2012/09/study-a-setback-for-the-obesity-vaccine/262487/