Comparative study of the lipogenic potential of human and rat adipose tissue

The reported low activity of lipogenic enzymes (especially adenosine tripho sphate [ATP]-citrate lyase) in human adipose tissue led to the general conc lusion that in humans lipogenesis occurs primarily in the liver. However, r ecent studies indicate that the liver plays a minor role in de novo lipogen esis and suggest that adipose tissue may be the principal lipogenic human t issue. In an attempt to resolve these contradictions we reinvestigated the lipogenic potential of human adipose tissue and compared with adipose tissu e of rats fed a high-fat diet for 2 weeks and fasted overnight before death . These conditions mimic the nutritional state of patients at the moment of tissue sampling. We found that overnight fasting of the rats maintained pr eviously for 12 days on a high-fat diet caused a decrease of ATP-citrate ly ase of about 7-fold. Thus, in human adipose tissue, the mean activity of AT P-citrate lyase was approximately 8 times lower than in rats fed a high-fat diet and fasted overnight, and about 50 times lower than in rats maintaine d on normal laboratory diet. Unlike ATP-citrate lyase, fatty acid synthase (FAS) activity was only slightly lower in human adipose tissue than in rats maintained on a normal laboratory diet. Comparable FAS activity was found when rats were fed a high-fat diet and fasted overnight. The average activi ties of human adipose tissue acetyl-coenzyme A carboxylase, malic enzyme, a nd glucose-6-phosphate dehydrogenase were approximately 3-, 4-, and 6-fold lower than in adipose tissue from rats fed a high-fat diet and fasted overn ight before tissue sampling, while the activity of 6-phosphogluconate dehyd rogenase in humans was higher than in rat adipose tissue. No significant di fferences in lipogenic enzyme activities were found between male and female and between lean and obese patients. The rate of fatty acid synthesis in i ntact pieces of human adipose tissue was approximately 5 times lower than i n adipose tissue pieces of rats fed a high-fat diet and fasted overnight be fore tissue samples were taken. The comparison of the lipogenic potential o f humans and rats (maintained on the diet to mimic the nutritional state of patients at the time of tissue sampling) suggests that human adipose tissu e is an important site of fatty acid synthesis. Copyright (C) 2000 by W.B. Saunders Company.