出版社：American Society for Biochemistry and Molecular Biology
摘要：Increased triglyceride synthesis resulting from enhanced fluxof fatty acids into liver is frequently associated with VLDLoverproduction. This has led to the common belief that hepatictriglyceride synthesis can directly modulate VLDL production.We used adenoviral vectors containing either murine acyl-coenzymeA:diacylglycerol transferase 1 (DGAT1) or DGAT2 cDNA to determinethe effect of a short-term increase in hepatic triglyceridesynthesis on VLDL triglyceride and apolipoprotein B (apoB) productionin female wild-type mice. Hepatic DGAT1 and DGAT2 overexpressionresulted in 2.0-fold and 2.4-fold increases in the triglyceridecontent of liver, respectively. However, the increase in hepatictriglyceride content had no effect on the production rate ofVLDL triglyceride or apoB in either case. Liver subfractionationshowed that DGAT1 and DGAT2 overexpression significantly increasedthe content of triglyceride within the cytoplasmic lipid fraction,with no change in the triglyceride content of the microsomalmembrane or microsomal VLDL. The increased cytoplasmic triglyceridecontent was observed in electron micrographs of liver sectionsfrom mice overexpressing DGAT1 or DGAT2. Overexpression of DGAT1or DGAT2 resulted in enhanced [3H]glycerol tracer incorporationinto triglyceride within cytoplasmic lipids. These results suggestthat increasing the cytoplasmic triglyceride pool in hepatocytesdoes not directly influence VLDL triglyceride or apoB production.In the presence of adequate cytoplasmic lipid stores, factorsother than triglyceride synthesis are rate-limiting for VLDLproduction.Supplementary key words cholesterol • low density lipoprotein • adenovirus • apolipoprotein B • diacylglycerol • acyl-coenzyme A:diacylglycerol transferase • very low density lipoprotein
Abbreviations: AdmDGAT1 or AdmDGAT2, recombinant adenovirus containing the murine DGAT1 or DGAT2 cDNA; AdNull, recombinant adenovirus containing no transgene; ALT, alanine aminotransferase; apoB, apolipoprotein B; DGAT, acyl-coenzyme A:diacylglycerol transferase; ER, endoplasmic reticulum; GFP, green fluorescent protein; MTP, microsomal triglyceride transfer protein
