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 induce hyperadiposity despite hypophagia associated with chemical ablation 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 neonatal MSG treatment. Male rat pups were injected with MSG or saline vehicle 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 measured and brains dissected for measurement of NPY content. By 30 days, NPY concentrations were reduced in the arcuate nucleus and anterior hypothalamus, and animals tended to be hypophagic. Peripheral adipose tissue levels were less than controls, in line with their low leptin concentrations. At 90 days, MSG treatment was associated with marked reductions in NPY concentrations in several hypothalamic areas, including the PVN and arcuate nucleus, along with increased adiposity and plasma leptin. Animals also displayed marked hypophagia. Levels of GLUT4 transporter were reduced in brown adipose tissue at both ages. The early decrease in brown fat GLUT4 suggests an impairment of the hypothalamic sympathetic input to brown fat which disrupts thermogenesis, contributing to the development of adiposity in the presence of hypophagia.