ENZYMES RELATED TO LIPOGENESIS IN ADIPOSE-TISSUE OF OBESE SUBJECTS

In a group of 10 adult obese subjects, maintained for 15 days on a normal caloric intake and balanced diet, the activity of hexokinase (EC 2.7.1.1), 6-phosphofructokinase (EC 2.7.1.11) and ATP citrate-lyase (EC 4.1.3.8) in the adipose tissue was significantly increased, both on a protein and on a fat cell number basis, compared to matched normal subjects. The activity of G-6-P dehydrogenase (EC 1.1.1.49), malate dehydrogenase (EC 1.1.1.37) and malate dehydrogenase (decarboxylating) (NADP) (EC 1.1.1.40) was unchanged. Since both hexokinase and 6-phosphofructokinase are rate-liniting in glycolysis, their enhanced activity would indicate the occurrence of an increased capacity to metabolize glucose and therefore to generate .alpha.-glycerophosphate. The elevation of ATP citrate-lyase would suggest increased lipogenesis, owing to the regulatory role that this enzyme plays in fatty acid synthesis. The normal activity of G-6-P dehydrogenase and malate dehydrogenase (decarboxylating) (NADP), which supply NADPH for the reduction of acetyl-CoA to fatty acids, would suggest that the change in lipogenesis is of moderate degree, thereby affecting only the most rate-limiting enzyme, ATP citrate-lyase. These data, on the whole, are consistent with the occurrence of enhanced triglyceride formation. Whether the enzyme changes observed are adaptive or genetic in nature remains to be clarified.