Peptide YY: obesity's cause and cure?

Abstract

RECENTLY, the United States Food and Drug Administration (FDA) decided for the present against approving the cannabinoid receptor antagonist Rimonabant® for the treatment of obesity in the United States. This decision mainly resulted from concerns based on study results showing that the drug’s benefits would not outweigh its risks for side effects. This decision further diminished already limited hopes, that a potent and safe anti-obesity drug would soon emerge and remove one of the most serious health threats to industrialized and developing societies of today and tomorrow. What would a new drug candidate have to become a perfect anti-obesity agent? Such a perfect anti-obesity molecule should not only lead to sustained loss of body fat, but also induce the necessary negative energy balance without causing undesired side effects. What’s more, a perfect anti-obesity agent would preferably be a naturally occurring, endogenous, molecule and it should target a known specific mechanism. Finally, it should remove the cause for obesity rather than treating symptoms of the disease. Looking at these requirements, it seems that such a silver bullet may already be available: the gastrointestinal hormone, peptide YY (PYY). Based on published data, peptide YY may be the only currently known molecule which matches these criteria without exception: PYY has been reported to induce a negative energy balance by potently decreasing food intake in rodents (1) and humans (2) without causing any undesired side effects (1,2). This gut peptide is a naturally occurring hormone which is secreted by endocrine L-cells of the colon (3). The reported mechanism of action of its predominantly circulating form, PYY3-36, is based on the