LIPOGENIC ENZYMES OF RAT-LIVER AND ADIPOSE-TISSUE - DIETARY VARIATIONS AND EFFECT OF POLYCHLORINATED-BIPHENYLS

The lipogenic enzymes fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzyme (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glu cose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluco nate dehydrogenase (PGDH; EC 1.1.1.44) were investigated in liver and in brown adipose tissue (BAT) of Wistar rats under various dietary con ditions and in the presence of 15 to 250 ppm (approximately 0.045-0.75 mu mol/kg chow) polychlorinated biphenyls (PCBs). In response to refe eding starved animals, enzyme activities in both tissues increased to above normal levels and thereafter exhibited pronounced oscillations o f their activities. The extent of increase depended on the carbohydrat e and fat content of the diet. The lipogenic enzymes could be grouped in two categories according to their sensitivity to dietary carbohydra te: FAS and CCE responded faster to smaller changes in dietary composi tion, while ME, G6PDH and PGDH required larger changes and more time t o respond. Diet-induced alterations of enzyme activities were of the s ame order of magnitude in liver and BAT. They were age-dependent, bein g more pronounced in young animals. Independent of the type of dietary manipulations, activities changed in a coordinate fashion, i.e., the changes of the activities of all 5 enzymes occurred at similar ratios to each other with an identical time course. Feeding PCB-containing di ets resulted in a considerable increase of the activities of the lipog enic enzymes in liver, which was significantly greater with ME, G6PDH and PGDH. The effect was dose-dependent but transient. In liver the re sponse to PCB feeding was identical in male and female animals, wherea s in BAT lipogenic activities increased in females, but decreased in m ales. Refeeding starved animals with a PCB-containing diet led to an a dditional stimulation of the normal refeeding-induced increase of the enzyme activities in liver and BAT. This PCB-induced increase was 2-fo ld for FAS and CCE, but up to 15-fold for the other enzymes. All PCB-i nduced effects were significantly less pronounced in old than in young animals. In primary hepatocytes activities increased in hormone-free medium in the presence of PCBs. While activity was induced in insuline - and triiodothyronine-containing medium, this increase was significan tly greater with PCBs present.