Metabolic regulation as a control for lipid disorders. II. Influence of (——)-hydroxycitrate on genetically and experimentally induced hypertriglyceridemia in the rat

Abstract

These studies were designed to determine whether genetically and experimentally induced hypertriglyceridemia were correlated with hyperlipogenesis, and whether inhibiting fatty acid synthesis would reduce serum triglyceride levels. Hypertrigylceridemia, resulting from genetic obesity in Zucker rats and fructose feeding or Triton administration to Charles River rats, was examined in relation to in vivo rates of heatic fatty acid synthesis, and the influence of (--)-hydroxycitrate (a potent competitive inhibitor of ATP citrate lyase) on serum triglyceride levels and lipogenesis was determined. Zucker obese rats demonstrated significantly increased rates of fatty acid synthesis and levels of serum triglycerides compared to their lean litter mates; lipogenic rates and circulating triglycerides were reduced markedly by the oral administration of (--)-hydroxycitrate. Fructose administered in the diet or drinking water induced a hypertriglyceridemia which was associated with a marked increase in hepatic lipogenesis, and (--)-hydroxycitrate reduced significantly both parameters. In contrast to the significant role that increased rates of lipogenesis apparently played in the development of hypertriglyceridemia in the Zucker rat and fructose-fed rat, Triton given intravenously produced a marked rise in serum triglycerides which could not be accounted for, to an appreciate extent, by increased rates of fatty acid synthesis. (--)-Hydroxycitrate reduced serum triglyceride levels and hepatic lipogenic rates equivalently in the Triton-treated and nontreated rats.