Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 286, Issue 6, Pages E1004-E1010Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00427.2003
Keywords
food intake; body weight; hypothalamus
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Funding
- NIDDK NIH HHS [DK-R01-40963] Funding Source: Medline
- NIMH NIH HHS [MH-63303] Funding Source: Medline
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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.
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