DEHYDROEPIANDROSTERONE AND BODY-FAT

Dehydroepiandrosterone sulfate (DHEA-S) is the mo st abundant circulat ing adrenal steroid in man, yet its physiologic role and that of its p arent compound DHEA are unknown, Age-related decreases in DHEA in asso ciation with increases in obesity, insulin resistance, and atheroscler osis are well known, Recent investigations in lower mammals (which do not secrete DHEA) have suggested that DHEA (or its metabolites) mag fu nction as an antiobesity agent in these models of obesity independent of food intake, Proposed mechanisms for the decrease in fat mass and l ower weight gain when DHEA is given orally include increases in futile cycling and peroxisomal beta-oxidation and decreases in de novo lipog enesis, Alterations in the availability of reducing equivalents for li pid synthesis do not appear to explain this decrease, Changes in pancr eatic insulin secretion or insulin sensitivity may also be responsible for some of these effects, Studies in humans have failed to demonstra te a beneficial effect of DHE A on bo dy composition or energy expendi ture at either pharmacologic or physiologic replacement doses for 1-3 months, Administration of DHEA to men or women has also not been shown to alter insulin sensitivity as measured by the minimal model or the euglycemic clamp technique. The effect of DHEA on peroxisomal beta-oxi dation and de novo lipogenesis is not known, We conclude that a signif icant role for DHEA in the pharmacologic treatment of human obesity is unlikely.