Studies on the Metabolism of Adipose Tissue: XIX. AN EVALUATION OF THE MAJOR PATHWAYS OF GLUCOSE CATABOLISM AS INFLUENCED BY ACETATE IN THE PRESENCE OF INSULIN

Abstract

Abstract Rat epididymal fat pads were incubated at 37° in bicarbonate buffer, pH 7.4, with glucose (10 mm) or with glucose plus acetate (15 mm), in the presence of insulin (1000 microunits per ml). The net gas exchange, total CO2 production, O2 consumption, glucose utilization, lactate and glycerol production, and radioactive carbon incorporation into CO2 and fatty acids were measured, with the use of matched pieces of tissue, in the presence of (a) uniformly labeled glucose-14C, (b) uniformly labeled glucose-14C plus unlabeled acetate, (c) unlabeled glucose and acetate-1,2-14C, and (d) glucose-6-14C and unlabeled acetate. The results permitted the estimation of the quantitative flow of glucose and acetate carbon into the major metabolic pathways of adipose tissue. It was found that when glucose and acetate were present together the flow of glucose carbon through the pentose cycle increased 83% and total fatty acid synthesis 60% above that seen with glucose alone. Part of the increased fatty acid synthesis was due to a greater flow of glucose carbon to acetyl coenzyme A, brought about entirely by the increased production of glyceraldehyde phosphate in the pentose cycle. It was calculated that the pentose cycle provided 65% of the reduced nicotinamide adenine dinucleotide phosphate needed for reduction to fatty acid of the acetyl-CoA formed from glucose, but that this cycle furnished all the extra reducing equivalents needed when acetate was also available as a precursor for fatty acid synthesis. This difference is attributed to the production of reduced coenzymes in the formation of acetyl-CoA from glucose but not from acetate. The conversion of a portion of these reduced coenzymes into NADPH for use in fatty acid synthesis, and the reaction of of the remainder with oxygen, are discussed. It is concluded that the rate of these reactions may limit conversion of glucose to fat in adipose tissue maximally stimulated by insulin. A limitation does not appear to be set by the rate at which any of the following processes can proceed: (a) glucose uptake, (b) NADPH formation by the pentose cycle, (c) conversion of acetyl-CoA to fatty acids, (d) consumption of oxygen and production of adenosine triphosphate.