Elucidation of the significance of seipin in adipocyte differentiation using KO rat-derived fibroblasts

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17991
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Jichi Medical University
• Principal Investigator: ebihara chihiro 自治医科大学, 医学部, 客員研究員 (90790915)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: seisin / ラット / 脂肪萎縮症

Outline of Final Research Achievements

BSCL2 was identified as the causative gene of congenital systemic lipoatrophy in 2001 and the applicant's group was the first to report BSCL2 dysgenesis in Japan. The BSCL2-encoded sepin is thought to be a two-fold transmembrane protein consisting of 398 amino acids, but it shows no homology to known proteins and its physiological significance is unknown. We have previously generated seipin knockout (SKO) rats and demonstrated that seipin is essential for the development and differentiation of adipose tissue. In the present study, we will elucidate the role of sapin in the process of adipocyte differentiation by using an experimental system to induce adipocyte differentiation using primary cultured rat skin fibroblasts derived from SKO rats. Elucidation of the molecular biological significance of seipin in adipocyte differentiation will not only lead to the treatment of congenital systemic lipodystrophy, but will also contribute to the development of adipocyte research.

Free Research Field

糖尿病、肥満

Academic Significance and Societal Importance of the Research Achievements

脂肪萎縮症は脂肪組織が減少あるいは消失する疾患の総称で、障害部位により全身性と部分性に分類される。また原因も様々で、全身性、部分性それぞれに、先天性と後天性が存在する。しかしながら、いずれの場合においても一定以上の脂肪組織が消失すると強いインスリン抵抗性を伴う糖尿病や高中性脂肪血症、脂肪肝など種々の糖脂質代謝異常を呈する。先天性全身性脂肪萎縮症患者の平均寿命は３０ー４０歳と言われ極めて予後不良である。脂肪細胞分化におけるセイピンの分子生物学的意義の解明は、先天性全身性脂肪萎縮症の治療に結びつくだけではなく、脂肪細胞研究の発展に広く寄与することが期待できる。