Functional roles of proline/arginine-rich end leucine-rich repeat protein (PRELP) in adipocytes

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09783
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Okayama University
• Principal Investigator: Eguchi Jun 岡山大学, 大学病院, 講師 (60616366)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: メタボリックシンドローム

Outline of Final Research Achievements

PRELP belongs to the family of leucine-rich repeat proteins, which are characterized by a series of adjacent leucine-rich motifs flanked by disulfide-bounded domains. In the present study, we show that PRELP expression is up-regulated in adipocytes of obesity mice. PRELP reduction in 3T3-L1 adipocytes leads to insulin-stimulated glucose uptake. To determine functions of PRELP, we generated adipocyte-specific PRELP transgenic mice. Adipose-specific overexpression of PRELP results in the development of adipose tissue fibrosis and insulin resistance on high fat diet without difference of body weight and adiposity. This phenotype is associated with increased inflammation and decreased insulin signaling in adipose tissue. Furthermore, we find that global Prelp deficient mice are protected from adipose tissue fibrosis and insulin resistance associated with high fat feeding. These data suggest that PRELP might play a key role in the development of adipose tissue remodeling in obesity.

Free Research Field

糖尿病代謝

Academic Significance and Societal Importance of the Research Achievements

メタボリックシンドロームにおいては体内に脂肪組織が過剰に蓄積し, 過剰に蓄積した脂肪組織中では, 慢性的に炎症が起こっている。この慢性炎症が脂肪組織の繊維化を誘導し, 全身のインスリン抵抗性, 種々の代謝異常を引き起こす。脂肪組織の繊維化を軽減, もしくは治癒させることは, 国民の健康維持、増進に有用である。そのためには, 脂肪組織の繊維化発症に関わる病態を解明する必要があるが, 未だ不明な点が多い。本研究は, Prelpが脂肪組織の繊維化発症に関与している可能性を示した。メタボリックシンドロームの有効な治療薬開発の糸口になる可能性がある。