Leptin is a circulating protein secreted by adipocytes which has profo
und feeding, metabolic, and neuroendocrine effects. Leptin receptors h
ave been localized to the hypothalamus, but the anatomic sites respons
ible for mediating the effects of circulating leptin have not been dem
onstrated. We report that systemic administration of leptin activates
nuclear groups in the ventrobasal hypothalamus, including the ventrome
dial, dorsomedial, and ventral premammillary hypothalamic nuclei. Lept
in also activated the parvicellular subdivisions of the paraventricula
r hypothalamic nucleus that; project to parasympathetic and sympatheti
c preganglionic neurons. Finally, leptin administration activated the
superior lateral parabrachial subnucleus, a nuclear group containing c
holecystokinin neurons that project to the ventrobasal hypothalamus. T
hese findings indicate that circulating leptin activates specific nucl
ear groups in the hypothalamus and brainstem known to regulate complex
physiological responses during times of substrate availability.