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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.

Abstract
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)
AuthorsJ E Akerlund, I Björkhem
JournalJournal of lipid research (J Lipid Res) Vol. 31 Issue 12 Pg. 2159-66 (Dec 1990) ISSN: 0022-2275 [Print] United States
PMID2090709 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cholestyramine Resin
  • Hydroxymethylglutaryl CoA Reductases
  • Cholesterol 7-alpha-Hydroxylase
Topics
  • Animals
  • Cholesterol 7-alpha-Hydroxylase (metabolism)
  • Cholestyramine Resin (pharmacology)
  • Drainage
  • Enzyme Activation
  • Hydroxymethylglutaryl CoA Reductases (metabolism)
  • Ligation
  • Liver (enzymology)
  • Lymph (metabolism)
  • Male
  • Rats
  • Rats, Inbred Strains
  • Thoracic Duct (surgery)

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