Downregulation of leptin by free fatty acids in rat adipocytes: Effects oftriacsin C, palmitate, and 2-bromopalmitate

Free fatty acid (FFA) has been reported to decrease leptin mRNA levels in 3 T3-L1 adipocytes. When using this cell line, it is difficult to determine t he protein levels because a very small amount of leptin is secreted into th e medium. The effect of FFA on leptin secretion from adipocytes has not yet been determined. In addition, in vivo studies have failed to demonstrate a FFA-induced decrease in plasma leptin levels. To clarify the effect of FFA on leptin production, we investigated the leptin protein level in the medi um and the mRNA level in primary cultured rat adipocytes treated with triac sin C, which is a potent inhibitor of acyl-coenzyme A (CoA) synthetase, pal mitate, and 2-bromoparmitate. Triacsin C (0 to 5 x 10(-5) mol/L) decreased leptin concentrations in the culture medium in a dose-dependent manner. Lep tin mRNA levels were decreased to 10% of the control in the presence of tri acsin C. The concentration of triacsin C needed to suppress leptin producti on was similar to the Ki value (approximate to 10(-5) mol/L) for inhibition of acyl-CoA synthetase. Both palmitate and 2-bromopalmitate decreased lept in concentrations but did not affect the triacsin C-induced decrease in lep tin additively. In conclusion, both protein and mRNA levels of leptin were decreased by triacsin C and FFA in primary cultured rat adipocytes. Our fin dings suggest that FFA is involved in the regulation of leptin production i n adipocytes. Copyright (C) 2000 by W.B. Saunders Company.