^*Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, Washington

Correspondence: Richard Palmiter, Department of Biochemistry, Howard Hughes Medical Institute, Box 357370, University of Washington, Seattle, WA 98195. E-mail: palmiter@u.washington.edu

^**The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4 January 2005; Accepted 21 June 2005.

Abstract

Objective: Signaling through adrenergic receptors (ARs) by norepinephrine (NE) and epinephrine (Epi) regulates weight gain when mice are fed a high-fat diet (HFD) by controlling diet-induced thermogenesis. Thus, one would predict that mice unable to make NE/Epi because of inactivation of the dopamine -hydroxylase gene (Dbh-null mice) would have a propensity to become obese. We characterized the response of Dbh-null and control mice to a HFD.

Research Methods and Procedures: Dbh-null and control mice were fed an HFD or a regular diet (RD) for 2 months. Body weight, adiposity, muscle triglyceride levels, and adipocyte size were measured, as were circulating leptin, adiponectin, triglyceride, glucose, and insulin levels. A glucose tolerance test was also preformed.

Results: Dbh-null mice gain weight normally on an HFD and have the same adiposity. Their serum triglyceride and leptin levels are normal, but adipocytes are 30% smaller than controls. Dbh-null mice maintain low blood glucose levels and glucose tolerance when exposed to the HFD in contrast to controls.

Discussion: Complete lack of NE/Epi does not predispose to obesity. Because mice lacking all three ARs become obese on an HFD, an imbalance of signaling through - and ARs seems to be responsible for obesity. Surprisingly, Dbh-null mice maintain glucose tolerance.