An additional role for insulin in the control of fatty acid synthesis independent of glucose transport

Abstract

Glucose conversion into pyruvate and fatty acids was studied in epididymal adipose tissue incubated in vitro from normal, 36-h-fasted and fasted–refed rats.Insulin at optimal concentrations caused a 30-fold increase in the rate of glucose incorporation into fatty acids and an increased lactate/pyruvate output rate. Pyruvate, lactate, and N,N,N′,N′,-tetramethyl-p-phenylenediamine (TMPD) addition to this incubation medium resulted in a further 20–75% increase in the rate of fatty acid synthesis as well as a further increase in the pyruvate concentration of the incubation medium. These results suggested that it was the decreased pyruvate concentration secondary to the elevated NADH/NAD+ of the cytoplasm which limited further glucose conversion to fatty acid.With glucose as substrate, TMPD caused the medium pyruvate concentration to be at least as high or higher than that seen with insulin in both nutritional states. However, fatty acid synthesis rates were eightfold greater with insulin. Insulin in the absence of glucose caused a twofold increase in the fatty acid synthesis from pyruvate at a medium concentration of 250 μM in normal and 25 mM in the 36-h-fasted rat. Therefore, insulin augments the rate of fatty acid synthesis both by increasing the supply of substrate (pyruvate) and also by directly increasing pyruvate incorporation into fatty acid by a mechanism distinct from the known stimulation of glucose transport.In fat pads from fasted–refed rats incubated in the absence of exogenous substrate, the rate of fatty acid synthesis was doubled by insulin. This occurred when the rate of pyruvate output was half that in the control condition. This also suggests that insulin stimulated pyruvate conversion to fatty acid in the absence of the known augmentation of glucose transport by insulin.