L-FABP T94A decreased fatty acid uptake and altered hepatic triglyceride and cholesterol accumulation in Chang liver cells stably transfected with L-FABP.
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.
Gao
Na
N
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, 410078, People's Republic of China.
Qu
Xia
X
Yan
Jin
J
Huang
Qi
Q
Yuan
Hao-Yong
HY
Ouyang
Dong-Sheng
DS
D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D004951:Esterification / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D050505:Mutant Proteins / Q000494:pharmacology; D020125:Mutation, Missense / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism*
D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D050505:Mutant Proteins; D014280:Triglycerides; D002784:Cholesterol