Norepinephrine- and epinephrine-deficient mice gain weight normally on a high-fat diet.

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 beta-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 approximately 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 betaARs become obese on an HFD, an imbalance of signaling through alpha- and betaARs seems to be responsible for obesity. Surprisingly, Dbh-null mice maintain glucose tolerance.