Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice

Liver Int. 2011 Jan;31(1):52-64. doi: 10.1111/j.1478-3231.2010.02361.x. Epub 2010 Oct 29.

Abstract

Background & aims: Bile acid (BA) pool size remains unchanged after cholecystectomy (XGB) but it circulates faster, exposing the enterohepatic system to an increased flux of BA. Triglyceride (TG) and BA metabolisms are functionally inter-related. We investigated whether ablation of the gallbladder (GB) modifies hepatic TG metabolism.

Methods: Male mice were subjected to XGB and fed a normal diet. In some experiments, mice received a 1% nicotinic acid diet to block lipolysis. Parameters of BA and TG metabolism, and microsomal triglyceride transfer protein (MTTP) activity were measured 1-2 months after XGB. Serum parameters, hepatic lipids and mRNA expression of genes of lipid metabolism were determined.

Results: BA pool size and synthesis were normal, but biliary BA secretion doubled during the diurnal light phase in XGB mice. Serum and hepatic TG concentrations increased 25% (P<0.02), and hepatic very-low-density lipoproteins (VLDL)-TG and apoB-48 productions increased 15% (P<0.03) and 50% (P<0.01), respectively, after XGB. Feeding a 1% nicotinic acid did normalize VLDL production. MTTP activity increased 15% (P<0.005) after XGB. Hepatic free fatty acid (FFA) synthesis and content, and mRNA levels of lipid metabolism-related genes remained normal in XGD mice.

Conclusions: XGB increased serum and hepatic TG levels, and VLDL production, which were restored to normal by nicotinic acid. The results suggest that FFA flux from adipose tissue to the liver is increased in XGB mice. They support the hypothesis that the GB has a role in the regulation of hepatic TG metabolism and that XGB may favour the accumulation of fat in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Oxidase / genetics
  • Animals
  • Apolipoproteins B / metabolism
  • Bile Acids and Salts / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cholecystectomy*
  • Cholesterol / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Fatty Acids, Nonesterified / metabolism
  • Gene Expression Regulation, Enzymologic
  • Lipolysis / drug effects
  • Lipoproteins, VLDL / blood
  • Lipoproteins, VLDL / metabolism*
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Niacin / administration & dosage
  • RNA, Messenger / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Time Factors
  • Triglycerides / blood
  • Triglycerides / metabolism*
  • Up-Regulation

Substances

  • Apob protein, mouse
  • Apolipoproteins B
  • Bile Acids and Salts
  • Carrier Proteins
  • Fatty Acids, Nonesterified
  • Lipoproteins, VLDL
  • RNA, Messenger
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • microsomal triglyceride transfer protein
  • Niacin
  • Cholesterol
  • Cytochrome P-450 CYP3A
  • Acyl-CoA Oxidase