NEUROPEPTIDE-Y IN HYPOTHALAMIC PARAVENTRICULAR NUCLEUS - A CENTER COORDINATING ENERGY-METABOLISM

Intracerebroventricular injection of neuropeptide Y (NPY) has two effects on energy metabolism in addition to increased feeding: decreased brown fat thermogenesis and increased white fat lipoprotein lipase (LPL) enzymatic activity. We hypothesized that the paraventricular nucleus (PVN) of the hypothalamus is the controlling neural site for these responses. We further hypothesized that NPY stimulation at PVN would reduce gene expression for the critical brown fat thermogenic protein, uncoupling protein (UCP), and increase gene expression for the key white fat storage enzyme, LPL. In the first experiment, three groups of rats received injections every 6 h for 24 h (5 injections total) into the PVN: 1) NPY (1 mu g/1 mu l injection) and ad libitum food; 2) NPY (1 mu g/1 mu l injection) and food restricted to control intake; 3) saline injection (1 mu l) and ad libitum food. Both NPY-treated groups showed significant reductions (P < 0.05) in brown fat UCP mRNA levels and marked stimulation of LPL mRNA levels relative to controls. In the second experiment, ment, four groups of seven rats had NPY injected into the PVN: 0 (vehicle control); 0.1 mu g; 0.5 mu g; and 1 mu g. Injections were made every 6 h for 24 h. There was a dose-related reduction in UCP mRNA produced by the NPY treatment. NPY treatment increased LPL mRNA, but a smooth dosing effect was not evident. The observation that NPY in the PVN can coordinate more than one component of energy metabolism is significant when considered with many reports of responsiveness of NPY activity in the arcuate nucleus-PVN neural circuit to perturbations of energy balance such as fasting and feeding, diabetes, and genetic obesity. Taken together, the observations suggest the presence of a highly organized and comprehensive control element for energy metabolism that reaches far beyond simple appetite control.