A Short Lesson in The Complexity of Appetite

sharma-obesity-guthormones2Just how complex the biology of appetite regulation is nicely demonstrated in a study by Julie Berg Schmidt and colleagues from Denmark, published in the American Journal of Physiology, in which they examined the effects of PYY3-36 and GLP-1 on energy intake, energy expenditure and appetite in overweight men.

As readers may know, GLP-1 and PYY3-36 are gut hormones released in response to food intake with central effects on satiety (among other functions).

In this study, the researchers infused these hormones either alone or in combination into otherwise healthy overweight volunteers randomized, double-blinded, placebo-controlled 4-arm crossover study.

Each infusion (on separate days) lasted 150 minutes, during the final 30 of which, the participants were  offered ad libitum meals.

While the infusion of the individual hormones had little effect on appetite or energy intake, the combined infusion of both hormones decreased spontaneous energy intake by 30%.

Incidentally, levels of both hormones are elevated after bariatric surgery.

This study points to one of the key challenge in developing effective pharmacotherapy for obesity – in a complex system with several hormones working synergistically, it is often not enough to block or increase the action of one part of the system.

This is why I predict that we may well require combinations of several drugs working together to effectively treat obesity.

This, by the way, is no different from hypertension or diabetes where we often have to combine several agents for optimal control.

Edmonton, AB

ResearchBlogging.orgSchmidt JB, Gregersen NT, Pedersen SD, Arentoft JL, Ritz C, Schwartz TW, Holst JJ, Astrup A, & Sjödin A (2014). Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure and appetite in overweight men. American journal of physiology. Endocrinology and metabolism PMID: 24735885