Elucidation of pathogenesis and development of therapy of lipodystrophy using human iPS cell-derived adipocytes

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293211
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: National Cardiovascular Center Research Institute (2015-2016); Kyoto University (2013-2014)
• Principal Investigator: Hosoda Kiminori 国立研究開発法人国立循環器病研究センター, 病院, 部長 (40271598)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Kazutoshi 京都大学, iPS細胞研究所, 講師 (80432326) ; YAMASHITA Jun 京都大学, iPS細胞研究所, 教授 (50335288) ; NAKAO Kazuki 東京大学, 医学研究科, 准教授 (20217657) ; Ebihara Ken 自治医科大学, 医学研究科, 准教授 (70362514) ; SONE Masakatssu 京都大学, 医学研究科, 特定准教授 (40437207) ; SAKURAI Hidetoshi 京都大学, iPS細胞研究所, 講師 (80528745) ; FUJIKURA Junji 京都大学, 医学研究科, 助教 (70378743) ; NOGUCHI Michio 京都大学, 医学研究科, 特定講師 (00432394)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: seipin / iPS細胞 / 脂肪細胞 / 脂肪萎縮症 / インスリン抵抗性

Outline of Final Research Achievements

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by marked scarcity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early-onset diabetes. Mutation of the BSCL2/SEIPIN gene causes congenital generalized lipodystrophy. iPS cells were generated from two patients with CGL. Upon adipogenic differentiation, BSCL2-iPS cells exhibited marked reduction of lipid droplet formation concomitant with diffuse cytoplasmic distribution of ADRP, compared with iPS cells from healthy individuals. Forced expression of BSCL2 not only rescued the lipid accumulation defects, but also restored cytoplasmic punctate localization of ADRP in BSCL2-iPS cells. Coimmunoprecipitation indicated SEIPIN interacted with ADRP.

Free Research Field

内分泌代謝内科学