The Effect of Drugs on Lipogenesis from Glucose and Palmitate in Human Adipose Tissue

Abstract

Several drugs were tested for their ability to inhibit lipogenesis in human adipose tissue. Only fenfluramine was found to inhibit the incorporation of T-palmitate and ¹⁴C-glucose into neutral lipid in intact tissue. This effect was observed at drug concentrations above 1 mM. Fenfluramine inhibited lipogenesis in broken-cell preparations of human adipose tissue at concentrations of 1 mM and above. However, in this system the N-benzoyloxyethyl derivative of fenfluramine, S. 1513, was also found to inhibit lipogenesis. This drug was more potent than fenfluramine, a significant inhibition being observed at 0.4 mM During inhibition of lipogenesis in homogenates of adipose tissue by fenfluramine radioactitivity was found to accumulate in long-chain acyl-CoA which suggests that the drug may interfere with acylation of glycerol 3-phosphate. Evidence that fenfluramine may have a similar effect in vivo was considered, but the results were not statistically significant.