OR45-5 Cortisol Responsiveness to ACTH Predicts Metabolic Responses to Stress

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR45-HPA Axis
Basic/Translational
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 10:15 AM
Room 135 (Moscone Center)
Kevin Tao-kwang Lee*1, Iain J Clarke2 and Belinda Anne Henry1
1Monash University, Victoria, Australia, 2Monash University, Australia
Humans characterized as high cortisol responders consume more calories in response to stress than low cortisol responders1.  We have identified sheep that have either high (HR) or low (LR) cortisol responses to Synacthen (ACTH ) and shown that HR have a greater propensity to become obese2. This is associated with reduced skeletal muscle thermogenesis in HR2. The aim of the current study was to quantify physiological responses to various stressors in female HR and LR sheep (n = 5/group).  We measured resting plasma cortisol levels (10 min samples; 0900-1500h) and responses to corticotropin-releasing factor (CRF: 0.2µg/kg, i.v.). Basal levels of cortisol were similar, but cortisol responses to CRF were higher (P<0.05) in HR than LR (area under curve – AUC 155±25 ng/ml x minutes in HR and 72±12 ng/ml x minutes in LR). To test metabolic responses to stress in HR and LR, 3 stressors were applied and food intake and thermogenesis was monitored. Thermogenesis was recorded every 15 min with temperature recorders (Dataloggers, SubCue) implanted into skeletal muscle. Stressors were insulin-induced hypoglycaemia (IIG)(0.125 units/kg), a barking dog and an immune challenge (200ng/kg Lipopolysaccharide – LPS).  Blood samples were taken at 10min intervals to measure plasma levels of cortisol and glucose. IIG reduced (P<0.001) plasma levels of glucose to a similar degree in HR and LR (from 3.9 ± 0.1 to 2 ± 0.1 mmol/L in HR and LR). Similarly, both IIG and barking dog stress increased thermogenic output to a similar extent in HR and LR. Food intake after IIG was similar in LR and HR but barking dog stress reduced (p <0.01) food intake (by 13% ± 3%) in LR only.  LPS treatment increased cortisol levels in HR and LR but the effect was greater (P <0.05) in HR (AUC 1330 ± 126 ng/ml x minutes in HR and 1001 ± 88 ng/ml x minutes in LR). Food intake was reduced in both groups after LPS treatment, but to a greater (P<0.05) degree in LR (47% ± 7% in LR vs 26%±5% in HR).  LR animals had higher (P <0.05) temperature responses to LPS-challenge (AUC 20.4±1.9 °C x h in LR and 14.7±2.2°C x h in HR). Thus, exposure to stress reveals metabolic differences in HR and LR animals that may explain their differing propensity to become obese. Stress, especially LPS treatment, caused greater reduction in food intake and higher thermogenic output in LR, which would predispose to leaner body morphometry.

1 George SA et al (2010) Psychoneuroendocrinology 35:607. 2Henry BA & Clarke IJ (2012) Characterizing the cellular mechanisms of post-prandial thermogenesis in skeletal muscle. Joint Annual Meeting: ASN-ADSA-ASAS Joint Symposium, Phoenix Arizona. Abstract 8.

Nothing to Disclose: KTKL, IJC, BAH

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