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Am J Physiol Endocrinol Metab 286: E1004-E1010, 2004. First published January 28, 2004; doi:10.1152/ajpendo.00427.2003
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Catabolic action of insulin in rat arcuate nucleus is not enhanced by exogenous "tub" expression

Dianne P. Figlewicz,1,2 Aryana Zavosh,2 Timothy Sexton,3 and John F. Neumaier3

1Metabolism/Endocrinology, Veterans Affairs Puget Sound Health Care System, Seattle 98108; 2Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98195-6560; and 3Department of Psychiatry and Behavioral Sciences, University of Washington, Harborview Medical Center, Seattle, Washington 98104

Submitted 23 September 2003 ; accepted in final form 12 January 2004

The central nervous system (CNS) protein "tub" has been identified from the genetically obese "tubby" mouse. Although the native function of tub in situ is not understood, cell-based studies suggest that one of its roles may be as an intracellular signaling target for insulin. In normal animals, insulin acts at the hypothalamic arcuate nucleus (ARC) to regulate energy balance. Here we used a Herpes Simplex viral expression system to evaluate whether tub overexpression in the ARC of normal rats enhances this action of insulin. In chow-fed rats, tub overexpression had no effect on insulin action. In rats fed a high-fat diet snack in addition to chow, simulating the diet of Westernized societies, the body weight regulatory action of insulin was impaired, and tub overexpression further impaired insulin action. Thus an excess of tub at the ARC does not enhance the in vivo effectiveness of insulin and is not able to compensate for the "downstream" consequences of a high-fat diet to impair CNS body weight regulatory mechanisms.

food intake; body weight; hypothalamus


Address for reprint requests and other correspondence: D. Figlewicz Lattemann, VA Puget Sound Health Care System (151), 1660 So. Columbian Way, Seattle, WA 98108 (E-mail: latte{at}u.washington.edu).






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