In vitro inhibition of adipocyte lipogenesis in adipocytes exposed to serum from obese hyperleptinemic rats.

Abstract

Parabiosis studies between obese overfed rats and ad libitum-fed rats demonstrated the presence of a circulating factor produced by the obese rats that reduced body fat in the ad libitum partner by inhibiting lipogenic pathways. Subsequent in vitro studies showed that de novo lipogenesis was inhibited in adipocytes incubated for 12 h in the media containing 2% by volume serum from overfed obese rats. When leptin was discovered it was assumed that this was the “anti-lipogenic” factor (ALF) present in the serum from obese animals. Recently we have found that leptin does not inhibit lipogenesis in adipocytes in vitro. Since ALF is not present in serum from obese Zucker rats it appears that leptin is required for release of ALF. We have recently used malic enzyme activity as a measure of lipogenesis and find that serum from overfed obese rats inhibits enzyme activity in adipocytes but leptin alone (100 ng/ml) and serum from leptin-infused rats do not. Consistent with this observation, malic enzyme activity is not substantially reduced in adipose tissue from leptin-infused rats even though lipid synthesis is inhibited. We hypothesize that in conditions of obesity, leptin induces the release of a circulating factor that inhibits lipogenesis in mature adipocytes. The function of this factor is undefined, but it may influence the accumulation of lipid in different fat depots or it may prevent enlarged adipocytes from becoming unstable. Supported by Grant R01DK53903 awarded to RBSH.