title: Seipin ablation in mice results in severe generalized lipodystrophy.
abstract: Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is an autosomal recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance and fatty liver. Here, we create the first murine model of BSCL2 by targeted disruption of seipin, the causative gene for BSCL2. Compared with their wild-type littermates, the seipin(-/-) mice are viable and of normal weight but display significantly reduced adipose tissue mass, hepatic steatosis, glucose intolerance and hyperinsulinemia. The levels of leptin and adiponectin were both significantly decreased in seipin(-/-) mice, so were non-esterified fatty acids upon fasting. Surprisingly, however, hypertriglyceridemia which is common in human BSCL, was not observed in seipin(-/-) mice. Our findings suggest a possible tissue-autonomous role of seipin in liver lipid storage. The availability of the seipin(-/-) mice should help elucidate the molecular function of seipin and lead to a better understanding of the many metabolic consequences of human BSCL2.
authors.affiliation: Institute of Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing 100191, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cui
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Tang
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Liu
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Jingna
authors.initials: J
authors.lastname: Deng
authors.forename: Guoheng
authors.initials: G
authors.lastname: Xu
authors.forename: Xingui
authors.initials: X
authors.lastname: Peng
authors.forename: Shenghong
authors.initials: S
authors.lastname: Ju
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Yang
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D052497:Lipodystrophy, Congenital Generalized / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; D020738:Leptin