2020 Fiscal Year Final Research Report

Lysosome-related molecule myoferlin on macrophages in adipose inflammation associated with obesity

Research Project

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Project/Area Number	18K08476
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54040:Metabolism and endocrinology-related
Research Institution	Osaka University
Principal Investigator	Takami Yoichi 大阪大学, 医学系研究科, 助教 (90621756)
Co-Investigator(Kenkyū-buntansha)	樂木宏実大阪大学, 医学系研究科, 教授 (20252679) 中神啓徳大阪大学, 医学系研究科, 寄附講座教授 (20325369) 華山力成金沢大学, ナノ生命科学研究所, 教授 (40403191)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	myoferlin / マクロファージ / 脂肪炎症 / インスリン抵抗性 / 脂肪分化 / 肥満
Outline of Final Research Achievements	Whereas young MYOF KO mice on a normal diet showed aggravated glucose tolerance and insulin sensitivity, those on a HFD showed preserved glucose tolerance with an attenuated gain of body weight, reduced visceral fat deposits, and less severe fatty liver. Adipose MYOF expression was reduced by aging but was restored by an HFD along with retained expression of NFAT transcription factors. Knockdown of MYOF in preadipocytes suppressed proliferation and differentiation into mature adipocytes along with decreased expression of genes involved in adipogenesis. MYOF expression in preadipocytes was reduced with differentiation. Attenuated obesity in MYOF KO mice on an HFD was also accompanied with increased oxygen consumption by an unidentified mechanism and with reduced adipose inflammation due to less inflammatory macrophages. The multifunctional roles of MYOF involve the regulation of preadipocyte function and affect glucose metabolism bidirectionally depending on consumed calories.
Free Research Field	内分泌・代謝、老年内科
Academic Significance and Societal Importance of the Research Achievements	肥満およびそれに伴う代謝異常は心血管疾患の重要な危険因子であり、食生活の西洋化を認めるわが国においても社会問題の一つである。本研究において、我々はMYOFが脂肪細胞に発現し、前脂肪細胞の増殖や分化に関連し、若年年齢のMYOF KOにおいては部分型脂肪異栄養症様の表現型を呈する一方、高脂肪食負荷による肥満モデルにおいては肥満や糖代謝異常の抑制を認めることが明らかになった。また、MYOFは脂肪組織において摂取カロリーにより発現増加を認め、肥満病態においては増悪因子となる可能性が考えられた。これらのことは成人における肥満病態やそれに伴う代謝異常において治療標的分子になる可能性を示唆するものである。