L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP

Mol Cell Biochem. 2010 Dec;345(1-2):207-14. doi: 10.1007/s11010-010-0574-7. Epub 2010 Aug 20.

Abstract

Liver fatty acid-binding protein (L-FABP, FABP1) is a highly conserved key factor in lipid metabolism. This study was undertaken to verify whether the T94A mutation in the L-FABP gene affects fatty acid uptake and intracellular esterification into specific lipid pools. Candidate SNPs were recreated using site-directed mutagenesis and tested for physical function in stably transfected Chang liver cell lines. We found that the T94A mutant of L-FABP lowered FFA uptake but had no effect on FFA efflux. L-FABP T94A-expressing cells showed decreased triglyceride content and increased cholesterol accumulation compared to the wild-type control for cells incubated with an FFA mixture (oleate: palmitate, 2:1 ratio). In conclusion, our study provided additional indications of the functional relevance of the L-FABP T94A SNP in hepatic fatty acid and lipid metabolism in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cholesterol / metabolism*
  • Esterification / genetics
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / pharmacology*
  • Fatty Acids / metabolism*
  • Humans
  • Lipid Metabolism / drug effects
  • Liver / metabolism*
  • Mutant Proteins / pharmacology
  • Mutation, Missense / physiology
  • Polymorphism, Single Nucleotide / physiology
  • Transfection
  • Triglycerides / metabolism*

Substances

  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Mutant Proteins
  • Triglycerides
  • Cholesterol