title: Norepinephrine- and epinephrine-deficient mice gain weight normally on a high-fat diet.
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 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.
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Box 357370, University of Washington, Seattle, WA 98195, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Ste Marie
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.forename: Wendy
authors.initials: W
authors.lastname: Curtis
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: 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*
chemical_list: D004041:Dietary Fats; D011941:Receptors, Adrenergic; D009638:Norepinephrine; D004837:Epinephrine