THE EFFECT OF GAMMA-HEXACHLOROCYCLOHEXANE (LINDANE) ON THE ACTIVITIESOF LIVER LIPOGENIC ENZYMES AND ON SERUM-LIPIDS IN RATS

The effect of dietary gamma-hexachlorocyclohexane (lindane) (50-350 pp m, 0.17-1.19 mu mol/kg chow) on the activity of enzymes of lipogenesis , viz., fatty acid synthase (FAS; EC 2.3.1.85), citrate cleavage enzym e (CCE; EC 4.1.3.8), malic enzyme (ME; EC 1.1.1.40), glucose-6-phos ph ate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrog enase (PGDH; EC 1.1.1.44), and on serum lipid levels, was investigated in livers of 35-day-old male Wistar rats. Lindane (150 ppm) caused a substantial decline of enzyme activities within the first 24 h of trea tment. The decrease was transient, however, and enzyme activities subs equently recovered despite continuation of lindane feeding. The recove ry of enzyme activities was comparatively fast in the case of ME, G6PD H and PGDH, but very slow with FAS and CCE. Activities of lipogenic en zymes decrease when animals are starved, and increase much beyond pres tarvation levels upon subsequent refeeding. Lindane in the refeeding d iet blunted this overshoot of FAS and CCE activities in a dose-depende nt manner. In contrast, activities of ME, G6PDH and PGDH responded to low dietary lindane concentrations with a substantial stimulation of t he increase of activity, whereas at high lindane concentrations the ov ershoot was inhibited.According to their responses to lindane exposure , liver lipogenic enzymes could be grouped into 2 categories with FAS and CCE representing one and ME, G6PDH and PGDH representing the other group. Polychlorinated biphenyls (PCBs) in the diet caused basically opposite changes of the activities of the lipogenic enzymes. Go-admini stration of lindane and PCBs resulted in an apparent cancellation of e ffects, suggesting that lindane and PCBs affect fatty acid synthesis a t opposite points. Levels of the serum triglycerides were increased si gnificantly as a result of lindane feeding, while serum cholesterol an d phospholipid levels were only slightly elevated. The increase of ser um triglyceride levels that is routinely observed after refeeding of s tarved animals was stimulated even more by low concentrations of linda ne in the refeeding diet, but inhibited by high concentrations.