出版社：American Society for Biochemistry and Molecular Biology
摘要：Recent studies have examined the role of the LDL receptor (LDLR) in regulating murine hepatic lipoprotein production and apolipoprotein B (apoB) secretion, with divergent conclusions from in vivo versus in vitro approaches. We have re-examined this question, both in vivo and in vitro, using apobec-1 −/− mice to model the pattern of human hepatic apoB-100 secretion. Hepatic triglyceride production in vivo (using Triton WR-1339) was unchanged in wild-type (WT) C57BL/6, apobec-1 −/−, ldlr −/−, and [apobec-1 −/− , ldlr −/− ] mice, while apoB-100 production (using [35S]methionine incorporation) was increased >2-fold in [apobec-1 −/− , ldlr −/− ] mice. Although >90% of newly synthesized apoB floated within the d [apobec-1 −/− , ldlr −/− ] mice, but not WT, apobec-1 −/−, or ldlr −/− mice, distributed into smaller (intermediate and LDL-sized) particles. Studies in isolated hepatocytes from these different genotypes confirmed secretion of smaller particles exclusively from [apobec-1 −/− , ldlr −/− ] mice, and pulse-chase analysis demonstrated increased secretion of apoB-100 with virtual elimination of posttranslational degradation. These results directly support the suggestion that the LDLR regulates hepatic apoB-100 production and modulates secretion of small, triglyceride-rich particles, both in vivo and in vitro.
