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Am J Physiol Endocrinol Metab (January 28, 2004). doi:10.1152/ajpendo.00427.2003
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Submitted on September 23, 2003
Accepted on January 12, 2004

The Catabolic Action of Insulin in Rat Arcuate Nucleus is not Enhanced by Exogenous 'Tub' Expression

Dianne P. Figlewicz1*, Aryana Zavosh2, Timothy Sexton3, and John F. Neumaier3

1 Department of Metabolism/Endocrinology (151), VA Puget Sound Health Care System, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
2 Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
3 Department of Psychiatry and Behavioral Sciences, University of Washington, Harborview Medical Center, Seattle, WA, USA

* To whom correspondence should be addressed. E-mail: latte{at}u.washington.edu.

The central nervous system (CNS) protein 'tub' has been identified from the genetically obese 'tubby' mouse. While 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 to regulate energy balance. Here we used a Herpes Simplex viral expression system to evaluate whether 'tub' overexpression in the arcuate nucleus (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 arcuate nucleus 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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D. P. Figlewicz, J. L. Bennett, S. Aliakbari, A. Zavosh, and A. J. Sipols
Insulin acts at different CNS sites to decrease acute sucrose intake and sucrose self-administration in rats
Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2008; 295(2): R388 - R394.
[Abstract] [Full Text] [PDF]


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