| First Author | Wang M | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 461 |
| Issue | 2 | Pages | 206-10 |
| PubMed ID | 25866184 | Mgi Jnum | J:228386 |
| Mgi Id | MGI:5706886 | Doi | 10.1016/j.bbrc.2015.03.117 |
| Citation | Wang M, et al. (2015) Dysfunction of lipid metabolism in lipodystrophic Seipin-deficient mice. Biochem Biophys Res Commun 461(2):206-10 |
| abstractText | Congenital generalized lipodystrophy (CGL) is characterized by a complete loss of body adipose tissue accompanying dyslipidemia, severe hepatic steatosis and insulin resistance. However, the mechanisms of dyslipidemia and hepatic steatosis are unclear. Here using the lipodystrophic Seipin-deficient mouse (Seipin(-/-)) model, we found Seipin(-/-) mice were unable to respond appropriately to a long time fasting and developed postprandial hypertriglyceridemia. Impaired very low density lipoprotein (VLDL) secretion and enhanced triglyceride-rich lipoproteins (TRL) clearance were also observed in our Seipin(-/-) mice. To identify the association between upregulation of hepatic LDL receptor and enhanced TRL clearance, we crossed Seipin(-/-) mice with Ldlr(-/-) mice to generate Seipin(-/-)Ldlr(-/-) mice. Seipin(-/-)Ldlr(-/-) mice displayed increased TRL clearance only after 24 h-fast rather 6 h-fast. In contrast to Seipin(-/-) mice, Seipin(-/-)Ldlr(-/-) mice displayed hypertriglyceridemia as observed in human CGL patients. Furthermore, in this study, we demonstrated hepatic steatosis in lipodystrophy Seipin(-/-) mice is a metabolic adaptation of dysfunctional adipose tissue. This study using lipodystrophic model established the importance of adipose tissue in energy homeostasis and lipid metabolism. |