Mingming Gao1, Mengyu Wang1, Xin Guo1, Xu Qiu1, Lu Liu1, Jiawei Liao1, Jinjiao Liu1, Guotao Lu2, Yuhui Wang1, George Liu3. 1. Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China. 2. Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, 210093, China. 3. 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.
Abstract
OBJECTIVES: 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. METHODS AND 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. CONCLUSION: Our study demonstrates that expression of seipin in adipose tissue alone could rescue dyslipidemia, lipodystrophy, hepatic steatosis and insulin resistance in SKO mice.
OBJECTIVES: 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. METHODS AND RESULTS:Transgenic mice with adipose-specific expression of humanseipin 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. CONCLUSION: Our study demonstrates that expression of seipin in adipose tissue alone could rescue dyslipidemia, lipodystrophy, hepatic steatosis and insulin resistance in SKO mice.
Authors: L Dollet; J Magré; M Joubert; C Le May; A Ayer; L Arnaud; C Pecqueur; V Blouin; B Cariou; X Prieur Journal: Sci Rep Date: 2016-10-17 Impact factor: 4.379
Authors: George D Mcilroy; Karla Suchacki; Anke J Roelofs; Wulin Yang; Yanyun Fu; Bo Bai; Robert J Wallace; Cosimo De Bari; William P Cawthorn; Weiping Han; Mirela Delibegović; Justin J Rochford Journal: Mol Metab Date: 2018-01-31 Impact factor: 7.422