title: Dysfunction of lipid metabolism in lipodystrophic Seipin-deficient mice.
abstract: 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.
authors: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors: Mengyu
authors: M
authors: Wang
authors: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors: Mingming
authors: M
authors: Gao
authors: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors: Jiawei
authors: J
authors: Liao
authors: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors: Yingchun
authors: Y
authors: Han
authors: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, China.
authors: Yuhui
authors: Y
authors: Wang
authors: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, China. Electronic address: georgeliu@bjmu.edu.cn.
authors: George
authors: G
authors: Liu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D005215:Fasting; D044388:GTP-Binding Protein gamma Subunits; D017353:Gene Deletion; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006943:Hyperglycemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008060:Lipodystrophy / Q000150:complications / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D052497:Lipodystrophy, Congenital Generalized / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C115783:Bscl2 protein, mouse; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins
keywords: Adipose tissue; Hypertriglyceridemia; Lipid metabolism; Lipodystrophy; Seipin