REDUCED BAT FUNCTION AS A MECHANISM FOR OBESITY IN THE HYPOPHAGIC, NEUROPEPTIDE-Y DEFICIENT MONOSODIUM GLUTAMATE-TREATED RAT

Neuropeptide Y (NPY) exerts effects on food intake at the level of the paraventricular nucleus (PVN), which receives a dense projection from the arcuate nucleus. Monosodium glutamate (MSG) has been shown to ind uce hyperadiposity despite hypophagia associated with chemical ablatio n of the arcuate nucleus. We investigated the mechanism for the excess fat accumulation by studying the time course of changes in brain NPY content, food intake, leptin levels and BAT GLUT4 content after neonat al MSG treatment. Male rat pups were injected with MSG or saline vehic le on days 2, 4, and 6 and examined at 30 and 90 days. Plasma leptin, body mass, length, adipose tissue mass and brown fat GLUT4 were measur ed and brains dissected for measurement of NPY content. By 30 days, NP Y concentrations were reduced in the arcuate nucleus and anterior hypo thalamus, and animals tended to be hypophagic. Peripheral adipose tiss ue levels were less than controls, in line with their low leptin conce ntrations. At 90 days, MSG treatment was associated with marked reduct ions in NPY concentrations in several hypothalamic areas, including th e PVN and arcuate nucleus, along with increased adiposity and plasma l eptin. Animals also displayed marked hypophagia. Levels of GLUT4 trans porter were reduced in brown adipose tissue at both ages. The early de crease in brown fat GLUT4 suggests an impairment of the hypothalamic s ympathetic input to brown fat which disrupts thermogenesis, contributi ng to the development of adiposity in the presence of hypophagia. (C) 1998 Elsevier Science B.V. All rights reserved.