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Publication : Dysfunction of lipid metabolism in lipodystrophic Seipin-deficient mice.

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.
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