Archive | 2019
Links Between Glucocorticoid Responsiveness and Obesity
Abstract
Abstract Activation of the hypothalamo-pituitary adrenal (HPA) axis and the secretion of glucocorticoids influences energy homeostasis via effects on food intake and energy expenditure. Furthermore, abdominal obesity is associated with hyperactivity of the HPA axis, which is driven by impaired glucocorticoid negative feedback. Recent data, however, suggests that altered glucocorticoid secretion may precede the onset of obesity. In any given population, there is great variation in the glucocorticoid secretory response to stress, with individuals identified as either high (HR) or low responders (LR). Sheep characterised as HR, have relatively increased food intake in response to stress, impaired satiety in response to melanocortin treatment and reduced energy expenditure. The reduction in energy expenditure in HR is due to diminished thermogenesis in skeletal muscle and decreased physical activity. This complex physiological phenotype is associated with increased propensity to become obese in HR animals. This chapter describes the metabolic, neuroendocrine and behavioural phenotype in ewes characterised as LR and HR. We propose that altered expression of key hypothalamic genes underpin the metabolic, thermogenic and behavioural sequelae associated with increased weight gain and increased susceptibility to become obese in HR compared to LR animals. The work described herein suggests that innate variation in cortisol responsiveness precedes weight gain and may be a marker to identification individuals at increased risk of becoming obese.