Overview: biology of regional fat distribution

Visceral obesity predicts non-insulin-dependent diabetes mellitus, cardiovascular disease, and stroke and is associated statistically with the established metabolic risk factors of these diseases. The condition shows several endocrine abnormalities in which a hypersensitive hypothalamo-adrenal axis seems to be a prominent feature. This axis responds to challenges at central, pituitary, and adrenal levels with elevated, protracted cortisol secretion, but it is not necessarily abnormally active in steady-state conditions, suggesting consequences of central, depressive responses to perceived stress with diminished feed-forward inhibition of cortisol secretion. There is suggestive evidence for serotonergic involvement including regulation of both corticotropin-releasing factor and appetite. Other hormonal abnormalities in the hypothalamo-gonadal and growth hormone axes might be secondary consequences. The multiple hormonal abnormalities provide possible explanations for both cardinal symptoms of the condition:insulin resistance and disproportional visceral accumulation of depot fat. Insulin resistance is a well-known consequence of hypercortisolemia but may also be caused by low sex steroid hormone secretions, and is probably amplified by free fatty acids from lipolytically active central depots. Visceral fat accumulation seems to be a result of the hormonal abnormalities via combined effects of elevated cortisol and insulin to accumulate triglycerides, whereas testosterone and growth hormone have opposite effects. Consequently low levels of the latter hormones will facilitate triglyceride accumulation. These events are probably more pronounced in visceral than other fat depots because of combined effects of high densities of adipocytes, specific steroid hormone receptors, and innervation as well as a high blood flow, resulting in a depot with a rapid turnover. The hyperactivity of the hypothalamo-adrenal axis suggests influence of perceived stress on susceptible personalities, a supposition supported by findings of associated psychosomatic and psychiatric disease, with depressive traits. There is also evidence for psychosocial and socioeconomic handicaps, and influence of smoking and alcohol consumption, which might provide background factors.