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Hyperphagia and Weight Gain after Gold-Thioglucose: Relation to Hypothalamic Neuropeptide Y and Proopiomelanocortin¹

Department of Human Anatomy and Cell Science, University of Manitoba (H.T.B., J.T.), Winnipeg, Manitoba, Canada R3E 0W3; and the Fishberg Center in Neurobiology, Mt. Sinai School of Medicine (T.M., C.V.M.), New York, New York 10029

Address all correspondence and requests for reprints to: Dr. Hugo T. Bergen, Department of Human Anatomy and Cell Science, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada R3E 0W3. E-mail: hbergen{at}cc.umanitoba.ca

Genetic obesity is associated with increased neuropeptide Y (NPY) messenger RNA (mRNA) and decreased POMC mRNA in the hypothalamus of ob/ob and db/db mice, or impaired sensitivity to MSH (derived from POMC) in the yellow agouti mouse. Acquired obesity can be produced by chemically lesioning the hypothalamus with either monosodium glutamate (MSG) in neonates or gold thioglucose (GTG) in adult mice. The present study examined whether elevated NPY mRNA and/or decreased POMC mRNA in the hypothalamus are associated with obesity due to hypothalamic lesions. GTG injection into adult mice produced a profound obese phenotype, including hyperphagia, increased body weight, and increased leptin mRNA and peptide, in association with reduced hypothalamic NPY mRNA and POMC mRNA. MSG treatment produced virtual elimination of NPY mRNA in the arcuate nucleus and a reduction of hypothalamic POMC mRNA, and led to elevated leptin. MSG pretreatment did not attenuate GTG-induced hyperphagia and obese phenotype. These results do not support a role for NPY-synthesizing neurons in the arcuate nucleus in mediating hypothalamic acquired obesity, but are consistent with the hypothesis that decreased activity of hypothalamic neurons synthesizing POMC play a role in mediating hypothalamic obesity.

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