Johannes D. Veldhuis, MD


March 15, 2000

In This Article

Leptin, Obesity, and Aging

Body mass index increases and visceral fat accumulates with age until early senescence. Levels of the nutritional signaling peptide leptin (mostly produced in white adipose tissue) increase pari passu. Leptin conveys signals to the hypothalamus about fat stores and, in response, hypothalamic efferents regulate food intake and energy expenditure.

Leptin inhibits the hypothalamic release of the orexigenic (appetite-inducing) peptide neuropeptide Y (NPY) and activates the sympathetic nervous system. The latter stimulates lipolysis in adipose tissue via the beta-3 adrenergic receptor, cAMP accumulation, and increased activity of mitochondrial uncoupling protein (UCP)-3, thus generating heat (which is dissipated) rather than ATP (which is stored).

In older animals, fasting suppresses circulating leptin concentrations and stimulates hypothalamic NPY secretion less effectively. In older rodents, leptin infusions also fail to augment energy expenditure as prominently. Thus, leptin-receptor signaling may be attenuated in aging.[23]