title: Identification of body fat mass as a major determinant of metabolic rate in mice.
abstract: OBJECTIVE
  Analysis of energy expenditure (EE) in mice is essential to obesity research. Since EE varies with body mass, comparisons between lean and obese mice are confounded unless EE is normalized to account for body mass differences. We 1) assessed the validity of ratio-based EE normalization involving division of EE by either total body mass (TBM) or lean body mass (LBM), 2) compared the independent contributions of LBM and fat mass (FM) to EE, and 3) investigated whether leptin contributes to the link between FM and EE.
  
  
  METHODS
  We used regression modeling of calorimetry and body composition data in 137 mice to estimate the independent contributions of LBM and FM to EE. Subcutaneous administration of leptin or vehicle to 28 obese ob/ob mice and 32 fasting wild-type mice was used to determine if FM affects EE via a leptin-dependent mechanism.
  
  
  RESULTS
  Division of EE by either TBM or LBM is confounded by body mass variation. The contribution of FM to EE is comparable to that of LBM in normal mice (expressed per gram of tissue) but is absent in leptin-deficient ob/ob mice. When leptin is administered at physiological doses, the plasma leptin concentration supplants FM as an independent determinant of EE in both ob/ob mice and normal mice rendered leptin-deficient by fasting.
  
  
  CONCLUSIONS
  The contribution of FM to EE is substantially greater than predicted from the metabolic cost of adipose tissue per se, and the mechanism underlying this effect is leptin dependent. Regression-based approaches that account for variation in both FM and LBM are recommended for normalization of EE in mice.
authors.affiliation: Department of Dental Public Health Sciences, School of Dentistry, University of Washington, Seattle, Washington, USA. kkaiyala@u.washington.edu
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Kaiyala
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
authors.forename: Brian G
authors.initials: BG
authors.lastname: Leroux
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogimoto
authors.forename: Brent
authors.initials: B
authors.lastname: Wisse
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism; D012044:Regression Analysis
chemical_list: D020738:Leptin