Promotion of hepatic lipid oxidation and gluconeogenesis as a strategy for appetite control

Abstract

There is considerable evidence that hepatic vagal afferents monitor the availability of liver glycogen and glucose metabolites, and that this mechanism participates in appetite regulation. Thus, promotion of gluconeogenesis and liver glycogen storage may enhance satiety. Hepatic lipid oxidation drives gluconeogenesis by positive allosteric modulation of pyruvate carboxylase and fructodiphosphatase. The rate-limiting enzyme for hepatic lipid oxidation, carnitine acyltransferase I, is activate by exogenous carnitine, and inhibited by malonyl coA. The lipogenesis inhibitor (−)-hydroxycitrate — a natural fruit acid found in the Brindall berry — can decrease production of malonyl coA in hepatocytes by potent inhibition of citrate lyase; many studies demonstrate that (−)-hydroxycitrate can reduce body fat accumulation in growing rats, owing in large part to a reduction in appetite. Joint administration of (−)-hydroxycitrate and carnitine should therefore promote hepatic lipid oxidation, gluconeogenesis, and satiety. Thermogenic effects as well as a reduction of the respiratory quotient can also be predicted. If this technique proves clinically useful in weight management, it could be used in conjunction with chromium picolinate and soluble fiber supplements, which appear to aid hunger control at the level of the hypothalamus and terminal ileum, respectively.