Metabolic regulation as a control for lipid disorders. I. Influence of (--)-hydroxycitrate on experimentally induced obesity in the rodent.

The feasibility of treating obesity by metabolic regulation has been explored in this study by examining the effect of (--)-hydroxycitrate on three types of experimentally induced obesity in the rodent.(--)-Hydroxycitrate was utilized because it depressed fatty acid and cholesterol synthesis in vivo through its activity as a potent competitive inhibitor of APT citrate lyase. In all models, the mature rat, the goldthioglucose-induced obese mouse, and the ventromedial hypothalmic lesioned obese rat, food intake and body weight gain were reduced signficantly by the chronic oral administration of a nontoxic dose of (--)-hydroxcitrate. Body composition analyses of mature rats treated with (--)-hydroxycitrate demonstrated a significant depression of body lipid levels and an unaltered body protein content. However, a citrate administration produced no significant effects on weight gain, food intake, or body lipid or protein levels when compared to controls.