title: Increased energy expenditure and leptin sensitivity account for low fat mass in myostatin-deficient mice.
abstract: Myostatin deficiency causes dramatically increased skeletal muscle mass and reduced fat mass. Previously, myostatin-deficient mice were reported to have unexpectedly low total energy expenditure (EE) after normalizing to body mass, and thus, a metabolic cause for low fat mass was discounted. To clarify how myostatin deficiency affects the control of body fat mass and energy balance, we compared rates of oxygen consumption, body composition, and food intake in young myostatin-deficient mice relative to wild-type (WT) and heterozygous (HET) controls. We report that after adjusting for total body mass using regression analysis, young myostatin-deficient mice display significantly increased EE relative to both WT (+0.81 ± 0.28 kcal/day, P = 0.004) and HET controls (+0.92 ± 0.31 kcal/day, P = 0.005). Since food intake was not different between groups, increased EE likely accounts for the reduced body fat mass (KO: 8.8 ± 1.1% vs. WT: 14.5 ± 1.3%, P = 0.003) and circulating leptin levels (KO: 0.7 ± 0.2 ng/ml vs. WT: 1.9 ± 0.3 ng/ml, P = 0.008). Interestingly, the observed increase in adjusted EE in myostatin-deficient mice occurred despite dramatically reduced ambulatory activity levels (-50% vs. WT, P < 0.05). The absence of hyperphagia together with increased EE in myostatin-deficient mice suggests that increased leptin sensitivity may contribute to their lean phenotype. Indeed, leptin-induced anorexia (KO: -17 ± 1.2% vs. WT: -5 ± 0.3%) and weight loss (KO: -2.2 ± 0.2 g vs. WT: -1.6 ± 0.1, P < 0.05) were increased in myostatin-deficient mice compared with WT controls. We conclude that increased EE, together with increased leptin sensitivity, contributes to low fat mass in mice lacking myostatin.
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, Diabetes and Obesity Center of Excellence, Seattle, WA 98109, USA.
authors.forename: Sun Ju
authors.initials: SJ
authors.lastname: Choi
authors.forename: Zipora
authors.initials: Z
authors.lastname: Yablonka-Reuveni
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Kaiyala
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogimoto
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schwartz
authors.forename: Brent E
authors.initials: BE
authors.lastname: Wisse
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D001823:Body Composition / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D002153:Calorimetry, Indirect; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005951:Glucose Tolerance Test; D020738:Leptin / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D055435:Myostatin / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D010101:Oxygen Consumption / Q000502:physiology; D012044:Regression Analysis
chemical_list: D020738:Leptin; D055435:Myostatin