title: Expression of seipin in adipose tissue rescues lipodystrophy, hepatic steatosis and insulin resistance in seipin null mice.
abstract: OBJECTIVE
  Gene mutations in an ER protein seipin result in congenital generalized lipodystrophy (CGL) in humans, accompanied with hepatic steatosis and insulin resistance. Seipin gene is highly expressed in the brain, testis and adipose tissue. Seipin globally deficient mice (SKO) displayed similar phenotypes as human counterparts. It has been demonstrated that adipose-specific seipin knockout mice at elder age were indistinguishable from SKO mice. Due to the large mass of adipose tissue in the body, we hypothesized that seipin in adipose tissue might be responsible for the multiple metabolism-related abnormalities in SKO mice.
  
  
  RESULTS
  Transgenic mice with adipose-specific expression of human seipin gene driven by aP2 promoter were generated and crossed with SKO mice to obtain adipose-specific seipin reconstitute (Seipin-RE) mice. In comparison with wild-type (WT) and SKO mice, the Seipin-RE mice exhibited normal plasma triglyceride and non-esterified fatty acids upon fasting, recovered adipose tissue mass, restored epididymal and subcutaneous fat pads morphology and partially recovered plasma leptin and adiponectin levels. Moreover, hepatic steatosis and insulin resistance was also absent in these mice.
  
  
  CONCLUSIONS
  Our study demonstrates that expression of seipin in adipose tissue alone could rescue dyslipidemia, lipodystrophy, hepatic steatosis and insulin resistance in SKO mice.
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Liao
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Jinjiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, 210093, China.
authors.forename: Guotao
authors.initials: G
authors.lastname: Lu
authors.affiliation: Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.forename: George
authors.initials: G
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005234:Fatty Liver / Q000517:prevention & control*; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D007333:Insulin Resistance; D008060:Lipodystrophy / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C115783:Bscl2 protein, mouse; D017931:DNA Primers; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins
keywords: Adipose-specific reconstitute mice; Global knockout mice; Seipin