Neuroendocrine abnormalities in human obesity.

Recent research has indicated that visceral obesity is associated with multiple endocrine disturbances. Insulin resistance, as well as visceral fat accumulation, may be consequences of these abnormalities. The complex endocrine aberrations are probably of central origin, and suggest a neuroendocrine background with a "hypothalamic arousal" syndrome. Such a syndrome has been found after excess alcohol intake, tobacco smoking, and certain types of stress reactions. Subjects with visceral obesity might be characterized by a high prevalence of such factors, although only indirect evidence is available for the stress component, maybe caused by a poor socioeconomic and psychosocial situation. In primate experiments, a submissive stress reaction is followed by a syndrome essentially identical to that seen in humans with visceral obesity, including visceral fat accumulation. These observations strongly support a similar chain of events in humans. Recent studies have indicated several abnormalities in cerebrospinal fluid (CSF) concentrations of catecholamines and neuropeptides. In particular, serotonin metabolites and corticotropin-releasing factor (CRF) concentrations are apparently lower than normal. In women with visceral obesity, these low concentrations are associated with food choices that indicate a preference for carbohydrates. This finding emphasizes the importance of serotonin agonists in the treatment of human obesity. It seems possible that such drugs may have effects on metabolic and other symptoms particularly prevalent in abdominal obesity, and that these effects might be independent of the decrease in energy intake. It would seem highly desirable to explore these possibilities further. Such observations may also provide a link between the abnormalities of low serotonin and CRF concentrations in the central nervous system on one hand and peripheral metabolic and other abnormalities on the other.