title: High cortisol responses identify propensity for obesity that is linked to thermogenesis in skeletal muscle.
abstract: Subjects characterized as cortisol high responders (HRs) consume more calories after stress, but it is unknown whether cortisol responsiveness predicts a propensity for obesity. Female sheep with either high or low cortisol responses to adrenocorticotropin (ACTH) were identified. Body composition was similar in HRs and cortisol low responders (LRs), but the HRs had greater (P<0.01) adiposity than did the LRs (40.5±0.7 vs. 35.8±1.4%) after high-energy feeding, despite comparable food intake. Postprandial thermogenesis in muscle temperature was 0.8 ± 0.08°C higher in the LRs than in the HRs (P<0.01), whereas feeding-induced changes in fat temperature were similar. Leptin and insulin sensitivity were similar in the HRs and LRs. Feeding lowered (P<0.001) the respiratory control ratio in muscle (HRs 9.2±0.8-5.2±1.2; LRs 8.4±0.5-5.2±0.7), indicative of increased uncoupled respiration. Also in muscle, the feeding-induced increases in uncoupling protein (UCP)-3 (fold increase: HRs, 2.4; LRs, 2.0), ryanodine 1 receptor (RyR1; fold increase: HRs 3.1; LRs 2.1), and sarcoendoplasmic reticulum Ca(2+)-dependent ATPase (fold increase: HRs 1.5; LRs 1.6) were equivalent in the HRs and LRs. Sequencing of mitochondrial DNA revealed no haplotypic differences between the 2 groups. We conclude that predisposition to obesity can be predicted by cortisol responsiveness to an ACTH challenge and that the response is due to innate differences in muscle thermogenesis.
authors.affiliation: 1Department of Physiology, Building 13F, Monash University, Clayton, VIC 3800, Australia. belinda.henry@monash.edu.
authors.forename: T Kevin
authors.initials: TK
authors.lastname: Lee
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Clarke
authors.forename: Justin
authors.initials: J
authors.lastname: St John
authors.forename: I Ross
authors.initials: IR
authors.lastname: Young
authors.forename: Brian L
authors.initials: BL
authors.lastname: Leury
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rao
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.forename: Belinda A
authors.initials: BA
authors.lastname: Henry
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012756:Sheep; D022722:Thermogenesis / Q000187:drug effects*
chemical_list: D020738:Leptin; D006854:Hydrocortisone
keywords: energy expenditure; hypothalamic-pituitary-adrenal axis; postprandial; stress