Adipocyte-specific ablation of mir221/222 protects mice from obesity and insulin resistance

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17984
• 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: Okayama University
• Principal Investigator: Yamaguchi Satoshi 岡山大学, 大学病院, 医員 (00834326)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: microRNA / メタボリックシンドローム / 糖尿病

Outline of Final Research Achievements

Adipose tissue specific miR-221/222 knockout mice were protected from diet induced obesity. Gene chip analysis of epididymal fat tissue and luciferase reporter assay revealed miR-221/222 target DNA-damage-inducible-transcript4(Ddit4). Ddit4 is known as a negative regulator of mechanistic target of rapamycin (mTOR) which positively regulate cell growth and proliferation. Ddit4 protein expression were enhanced in the epididymal fat of miR-221/222AdipoKO. MiR-221/222AdipoKO is protected from diet induced obesity through the repression of mTOR via miR-221/222 targeting Ddit4.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

脂肪細胞特異的miR-221/222ノックアウトマウスは食事誘導性肥満に抵抗性を示す事から、miR-221/222のメタボリックシンドロームにおける役割やその主たるターゲット遺伝子を明らかする事により、miR-221/222Antagomirが肥満症、2型糖尿病、メタボリックシンドロームに対する治療法となり得る。また、マウス、ヒト血清中のmiR-221/222濃度を検討する事により、糖尿病診断や予後予測のバイオマーカーとしての意義を検討する。