Sex differences in the response of several lipogenic enzymes to chronic ethanol ingestion

Abstract

The activities of glucose 6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase, NADP-malic dehydrogenase and ATP-citrate lyase have been measured in male and female Long-Evans rats fed both high-fat (34.2% of calories) and low-fat (4.6% of calories) liquid diets. Ethanol was incorporated into the diets by replacing 36% of the carbohydrate calories. Glucose 6-phosphate dehydrogenase activity was decreased by ethanol only in the males. A 40 per cent decrease was observed regardless of which diet was fed. Because ethanol affected this enzyme only in males, the phosphogluconate pathway may be more important in females during chronic ethanol metabolism. Ethanol had small and variable effects on isocitrate dehydrogenase, and the high-fat diet seemed to modify the differential response of this enzyme to ethanol between males and females. The NADP-malate dehydrogenase was decreased 57 per cent in males and 53 per cent in females after ethanol ingestion with the low-fat diet. With the high-fat diet, these decreases were more pronounced (74 and 68 per cent, respectively). Changes in the activity of ATP-citrate lyase have been said to parallel those of malate dehydrogenase; however, this was not observed in the female animals. Instead of decreasing, the activity of this enzyme increased in females after feeding ethanol with the low-fat diet. A kinetic analysis of the ATP-citrate lyase showed that the apparent V max had beenn altered, while the K m for citrate remained unchanged. These data suggest that ethanol may have altered the content of the enzyme in both males and females. The high-fat diet enhanced the effect of ethanol on the activity of this enzyme in males and tended to reverse the effect of ethanol in females. All of the above data suggest that lipogenesis may not be decreased in females as a result of ethanol and that sex hormones may play a role in the effects of ethanol on lipid metabolism in the rat.