| First Author | Moon BC | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 2 | Pages | 236-46 |
| PubMed ID | 22155452 | Mgi Jnum | J:195966 |
| Mgi Id | MGI:5486281 | Doi | 10.1161/ATVBAHA.111.241356 |
| Citation | Moon BC, et al. (2012) Apolipoprotein B secretion is regulated by hepatic triglyceride, and not insulin, in a model of increased hepatic insulin signaling. Arterioscler Thromb Vasc Biol 32(2):236-46 |
| abstractText | OBJECTIVE: States of insulin resistance, hyperinsulinemia, and hepatic steatosis are associated with increased secretion of triglycerides (TG) and apolipoprotein B (apoB), even though insulin targets apoB for degradation. We used hepatic-specific "phosphatase and tensin homologue deleted on chromosome 10" (Pten) knockout (hPten-ko) mice, with increased hepatic insulin signaling, to determine the relative roles of insulin signaling and hepatic TG in regulating apoB secretion. METHODS AND RESULTS: TG and apoB secretion was elevated in hPten-ko mice. When hepatic TG was reduced by inhibition of diacylglycerol acyltransferase 1/diacylglycerol acyltransferase 2 or sterol regulatory element-binding protein-1c, both TG secretion and apoB secretion fell without changes in hepatic insulin signaling. Acute reconstitution of hPten reduced hepatic TG content, and both TG and apoB secretion fell within 4 days despite decreased hepatic insulin signaling. Acute depletion of hepatic Pten by adenoviral introduction of Cre into Pten floxed mice caused steatosis within 4 days, and secretion of both TG and apoB increased despite increased hepatic insulin signaling. Even when steatosis after acute Pten depletion was prevented by pretreatment with SREBP-1c antisense oligonucleotides, apoB secretion was not reduced after 4 days. Ex vivo results were in primary hepatocytes were similar. CONCLUSIONS: Either hepatic TG is the dominant regulator of apoB secretion or any inhibitory effects of hepatic insulin signaling on apoB secretion is very short-lived. |
