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.


METHODS
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.


CONCLUSIONS
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.
Ste Marie
Linda
L
Department of Biochemistry, Howard Hughes Medical Institute, Box 357370, University of Washington, Seattle, WA 98195, USA.
Luquet
Serge
S
Curtis
Wendy
W
Palmiter
Richard D
RD
D017667:Adipocytes / Q000473:pathology; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D004837:Epinephrine / Q000172:deficiency*; D018149:Glucose Intolerance / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D009638:Norepinephrine / Q000172:deficiency*; D009765:Obesity / Q000503:physiopathology; D011941:Receptors, Adrenergic / Q000172:deficiency*; D022722:Thermogenesis / Q000502:physiology; D015430:Weight Gain / Q000502:physiology*
D004041:Dietary Fats; D011941:Receptors, Adrenergic; D009638:Norepinephrine; D004837:Epinephrine