Diminished Activities of Fatty Acid Synthesis Enzymes in Insulin-Resistant Adipocytes from Spontaneously Obese Rats

Abstract

Acetyl coenzyme A carboxylase and fatty acid synthetase activities were studied to determine the biochemical basis of the markedly impaired capacity of fat cells from spontaneously obese, old rats to convert glucose to fatty acids relative to cells from lean, young rats. Michaelis constants for the substrates of both enzymes were similar in large and small adipocyte homogenates. In contrast, V_max values were over 80% less in homogenates from large relative to small cells on a per cell basis. Long-term dialysis or the presence of albumin during the assays failed to restore the activities of these enzymes in homogenates of large fat cells. The combination of equal volumes of homogenates from the two cell types resulted in carboxylase and synthetase activities intermediate between activities found in the two homogenates alone. Therefore, the presence of endogenous allosteric inhibitors does not appear to account for the markedly blunted fatty acid synthesis enzyme activities in large fat cells. These results suggest that the fatty acid synthesis impairment, which is a primary defect in the insulin resistance of the large cells, is at least partly due to diminish ed cellular contents of acetyl coenzyme A carboxylase and fatty acid synthetase.

Key words

Insulin-Resistance - Isolated Adipocytes - Fatty Acid Synthesis - Fatty Acid Synthetase - Acetyl Coenzyme A Carboxylase