Neuroendocrine abnormalities in visceral obesity.
Central obesity is the subfraction which carries most of the risks for comorbidities. In this overview we suggest that this is due to neuroendocrine perturbations, where the hypothalamic-pituitary-adrenal (HPA) axis assumes a central role. The HPA axis is stimulated by central factors, which are often called stress. This is followed by discrete, periodical elevations of cortisol secretion during every day conditions. Such observations require diurnal measurements under undisturbed conditions. Saliva cortisol is useful for such purposes. It seems likely, based on cross-sectional observations in men and longitudinal studies in animals that a prolonged period of HPA axis stimulation is followed by a continuous degradation of the regulatory mechanisms. An end stage is a rigid cortisol secretion with low morning values. In parallel with this is a diminished function of the feed-back control as well as an inhibition of growth and sex steroid hormones. Evidence also suggests that the sympathetic nervous centers become activated in parallel. The net effects of this cascade of neuroendocrine-endocrine pertubations will be insulin resistance as well as visceral accumulation of body fat. These are effects of cortisol in combination with the diminished secretion of growth and sex steroid secretions, which in normal concentrations antagonize the cortisol effects. Blood pressure will also be elevated, which might be a consequence of central stimulation of the sympathetic nervous system, with added effects of insulin. What has developed is a hypothalamic arousal with the Metabolic Syndrome as a consequence. The feed-back regulation of the HPA axis has a key position in this chain of events. This control is mediated via glucocorticoid receptors in the lower parts of the brain. The gene for this receptor has shown polymorphisms which are associated with poorly regulated cortisol secretion, central obesity, insulin resistance and hypertension.
Björntorp
P
P
Department of Heart and Lung Diseases, Sahlgren's Hospital, University of Göteborg, Sweden. Per.Björntorp@Hjl.gu.se
Rosmond
R
R
D000311:Adrenal Glands / Q000503:physiopathology; D001824:Body Constitution; D005246:Feedback; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000503:physiopathology*; D009765:Obesity / Q000503:physiopathology*; D010902:Pituitary Gland / Q000503:physiopathology; D013312:Stress, Physiological / Q000503:physiopathology; D014781:Viscera