title: Stress-induced behavioral and metabolic adaptations lead to an obesity-prone phenotype in ewes with elevated cortisol responses.
abstract: The underlying cause of predisposition to obesity is complex but one marker is cortisol responsiveness. Selection of sheep for high (HR) or low (LR) cortisol responses to adrenocorticotropin shows that HR are more likely to become obese. Increased propensity to obesity is associated with reduced skeletal muscle thermogenesis. We sought to determine whether metabolic or behavioral responses to stress also contribute to altered propensity to obesity in LR and HR. Animals (n=5-10/group) were exposed to 3 stressors and we measured food intake and thermogenesis (recorded with dataloggers implanted into muscle). Stressors were hypoglycaemia (0.125 units/kg insulin, IV), a barking dog and immune challenge (200 ng/kg lipopolysaccharide--LPS, IV). LR animals showed a greater catabolic state in response to both immune and psychosocial stressors. LPS reduced (P<0.01) food intake in both groups but LR showed a greater (P<0.05) reduction in food intake and a more substantial (P<0.05) rise in muscle temperature. Introduction of the barking dog reduced (P<0.05) food intake in LR only. These metabolic differences coincided with differences in cortisol responsiveness, where HR animals had increased (P<0.05) cortisol in response to both immune and psychosocial stressors. We also assessed behavior in the following paradigms: 1, isolation in the open field test; 2, response to a human intruder; and 3, food competition. LR had greater (P<0.05) activity, reduced fearfulness and displayed a proactive coping style of behavior. Thus we demonstrate that high cortisol responsiveness identifies animals with stress-induced metabolic and behavioral traits that may contribute to susceptibility to obesity.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: T Kevin
authors.initials: TK
authors.lastname: Lee
authors.affiliation: CSIRO Animal, Food and Health Sciences, Armidale, NSW 2350, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Bischof
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia; Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Clarke
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3800, Australia. Electronic address: belinda.henry@monash.edu.
authors.forename: Belinda A
authors.initials: BA
authors.lastname: Henry
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000097:blood; D004435:Eating / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood*; D007003:Hypoglycemia / Q000097:blood; D009765:Obesity / Q000378:metabolism / Q000523:psychology*; D010641:Phenotype; D012756:Sheep / Q000097:blood / Q000378:metabolism / Q000523:psychology; D013315:Stress, Psychological / Q000097:blood / Q000378:metabolism*; D022722:Thermogenesis / Q000187:drug effects
chemical_list: D002395:Catecholamines; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: Energy balance; Hypothalamo-pituitary-adrenal axis; Lipopolysaccharide; Thermogenesis