Lipogenesis in human adipose tissue

Abstract

The pathways and some critical enzymes involved in lipogenesis in adipose tissue from 82 patients have been studied. Of the glucose-(14)C metabolized to lipid by isolated adipose cells, approximately 0.6% was recovered in fatty acids and the rest in glyceride-glycerol. Palmitate-1-(14)C was readily incorporated into neutral lipid. Homogenates of human adipose tissue contained an active alpha-glycerophosphate dehydrogenase which was approximately twice as active as malate dehydrogenase. Mitochondria of human adipose tissue contained an NAD-independent alpha-glycerophosphate dehydrogenase; the reaction product, di-hydroxyacetone phosphate, was recovered extramitochondrially. Homogenates of human adipose tissue also contained an active fatty acyl CoA synthetase which required ATP, CoA, and Mg(++) for maximal activity. The activity of acyl CoA synthetase varied greatly in a group of 40 patients. By contrast, the range of activity of malate dehydrogenase assayed in the same group of patients was much smaller. When palmitate or palmitoyl CoA was used as substrate, no difference was found in the rate of incorporation of alpha-glycerol-1,3-(14)C phosphate into neutral lipid. If time was allowed for activation of palmitate, the incorporation of alpha-glycerol-1,3-(14)C phosphate into lipid was 3.5 times greater than for unactivated palmitate. Palmitate (200 mM) stimulated lipogenesis in homogenates of human adipose tissue and then caused a severe inhibition at 700 mM. Arachidate over the same concentration range did not depress lipogenesis below initial values.