Studies on the regulation of cholesterol 7 alpha-hydroxylase and HMG-CoA reductase in rat liver: effects of lymphatic drainage and ligation of the lymph duct.
Lymphatic drainage leads to a significant stimulation of both the cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activity in rats (Björkhem et al. 1978. Biochem. Biophys. Res. Commun. 85: (532-540). This finding was confirmed here and it was also shown that ligation of the lymph duct leads to a similar but less pronounced effect. Ligation of the lymph duct or lymph fistulation of bile duct-ligated or cholestyramine-treated rats did not further increase 7 alpha-hydroxylase or the HMG-CoA reductase activity. However, treatment of lymph fistula rats with cholestyramine led to a significant further stimulation of both 7 alpha-hydroxylase and HMG-CoA reductase activity. Intravenous infusion of lymph into bile fistula rats led to a significant inhibition of both cholesterol 7 alpha-hydroxylase activity and HMG-CoA reductase activity. A corresponding infusion of cholesterol-enriched Intralipid led to inhibition of HMG-CoA reductase without effect on cholesterol 7 alpha-hydroxylase activity. The results show that cholesterol 7 alpha-hydroxylase is feedback-regulated by bile acids in a situation where the flux of cholesterol to the liver is interrupted also. The possibility is discussed that there is a factor in the lymph that down-regulates cholesterol 7 alpha-hydroxylase. If such a factor exists, it requires an intact enterohepatic circulation for its effect. The stimulatory effect of cholestyramine on HMG-CoA reductase also in lymph fistula rats shows that the previously demonstrated suppressive effect of bile acids on HMG-CoA reductase is not only due to the effect of bile acids on intestinal absorption of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
Akerlund
J E
JE
Department of Surgery, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden.
Björkhem
I
I
D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology; D004322:Drainage; D004789:Enzyme Activation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000201:enzymology*; D008196:Lymph / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013897:Thoracic Duct / Q000601:surgery
D002792:Cholestyramine Resin; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase