Cross-talk between sympathetic neurons and adipocytes in coculture

White adipose tissue plays an integral role in energy metabolism and is gov erned by endocrine, autocrine, and neural signals. Neural control of adipos e metabolism is mediated by sympathetic neurons that innervate the tissue. To investigate the effects of this innervation, an ex vivo system was devel oped in which 3T3-L1 adipocytes are cocultured with sympathetic neurons iso lated from the superior cervical ganglia of newborn rats. In coculture, bot h adipocytes and neurons exhibit appropriate morphology, express cell-type- specific markers, and modulate key metabolic processes in one another. Lipo lysis (stimulated by beta -adrenergic agents) and leptin secretion by adipo cytes are down-regulated by neurons in coculture, effects apparently mediat ed by neuropeptide Y (NPY). Secretion of NPY by neurons is up-regulated dra matically by the presence of adipocytes in coculture and appears to be medi ated by an adipocyte-derived soluble factor. Insulin, an antilipolytic agen t, down-regulates NPY secretion. Our findings suggest that an adipocyte-der ived factor(s) up-regulates the secretion of NPY by sympathetic neurons, wh ich, in turn, attenuates lipolytic energy mobilization by adipocytes.