title: Catabolic action of insulin in rat arcuate nucleus is not enhanced by exogenous "tub" expression.
abstract: 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.
authors.affiliation: Metabolism/Endocrinology, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA. latte@u.washington.edu
authors.forename: Dianne P
authors.initials: DP
authors.lastname: Figlewicz
authors.forename: Aryana
authors.initials: A
authors.lastname: Zavosh
authors.forename: Timothy
authors.initials: T
authors.lastname: Sexton
authors.forename: John F
authors.initials: JF
authors.lastname: Neumaier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000821:Animal Feed; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics*; D051381:Rats; D015203:Reproducibility of Results; D018139:Simplexvirus / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007004:Hypoglycemic Agents; D007328:Insulin; D011506:Proteins; C098988:Tub protein, mouse