The effect of gamma-hexachlorocyclohexane (lindane) on the activities of liver lipogenic enzymes and on serum lipids in rats.
The effect of dietary gamma-hexachlorocyclohexane (lindane) (50-350 ppm, 0.17-1.19 mumol/kg chow) on the activity of enzymes of lipogenesis, viz., 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), glucose-6-phosphate dehydrogenase (G6PDH; EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (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 treatment. The decrease was transient, however, and enzyme activities subsequently recovered despite continuation of lindane feeding. The recovery of enzyme activities was comparatively fast in the case of ME, G6PDH and PGDH, but very slow with FAS and CCE. Activities of lipogenic enzymes decrease when animals are starved, and increase much beyond prestarvation levels upon subsequent refeeding. Lindane in the refeeding diet blunted this overshoot of FAS and CCE activities in a dose-dependent manner. In contrast, activities of Me, G6PDH and PGDH responded to low dietary lindane concentrations with a substantial stimulation of the increase of activity, whereas at high lindane concentrations the overshoot 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. Co-administration of lindane and PCBs resulted in an apparent cancellation of effects, suggesting that lindane and PCBs affect fatty acid synthesis at opposite points.(ABSTRACT TRUNCATED AT 250 WORDS)
Boll
M
M
Abteilung Zellchemie, National Research Center for Environment and Health, München, Germany.
Weber
L W
LW
Stampfl
A
A
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004305:Dose-Response Relationship, Drug; D064429:Fatty Acid Synthases / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D008055:Lipids; D010743:Phospholipids; D014280:Triglycerides; D001556:Hexachlorocyclohexane; D002784:Cholesterol; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating); D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D064429:Fatty Acid Synthases; D001275:ATP Citrate (pro-S)-Lyase