Obesity hormones

Zofia Zukowska (Washington, DC) discussed the peripheral actions of neuropeptide Y (NPY), an important mediator by which diet and lack of physical activity lead to weight gain. NPY is synthesized as a 97 amino acid precursor, which is processed and amidated to NPY 1–36. NPY 1–36 is cleaved by dipeptidyl peptidase (DPP)-4 to NPY 3–36, which has other biologic activities, leading to the possibility that inhibitors of DPP-4 may potentiate NPY action with potentially adverse (or beneficial) effects. NPY is contained in all sympathetic nerves together with norepinephrine, although their modes of release are somewhat dissimilar. This is, then, a major sympathetic nervous system effector, elevated in stress, hypertension, cardiac and renal failure, and malignancies, which, Zukowska stated, is the most abundant peptide in the brain and heart. There are multiple G protein–coupled receptors for NPY including y1, which is vasoconstrictive, has atherogenic effects, and acts in the brain to reduce anxiety and increase appetite (1), and y2 and y5, which are also involved in the peptide's vascular effects (2). She cited evidence that although stress with increased sympathetic tone causes lipolysis by increasing catecholamine levels, sympathetic activation may also increase NPY, leading to angiogenesis and adipogenesis causing fat cell growth. Cold stress with a fat- and sugar-enriched diet increases body weight. An experimental model of daily 10-min encounters with an aggressive mouse was also associated with increased NPY as well as increased Y2 receptor expression, seen particularly with a high-fat diet and environmental stress. Interestingly, ob/ob mice have a sevenfold increase in NPY expression. NPY has insulin-like effects on release of adipokines and resistin. In vivo, NPY administration by a slow-release …