Project/Area Number |
17K09402
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Akita University |
Principal Investigator |
Nishijima Aki 秋田大学, 医学系研究科, 助教 (40566105)
|
Co-Investigator(Kenkyū-buntansha) |
戸田 修二 佐賀大学, 医学部, 教授 (80188755)
大森 泰文 秋田大学, 医学系研究科, 教授 (90323138)
山本 洋平 秋田大学, 医学部附属病院, 助教 (70400512)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 脂肪毒性 / 細胞外小胞 / エクソソーム / 内臓脂肪組織 / 皮下脂肪組織 / アディポソーム / 肝臓学 |
Outline of Final Research Achievements |
Adipose tissue (AT) is a major site of energy storage as well as an endocrine organ to regulate the metabolism. AT-based obesity is suggested to be closely associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD). We have established a method for analyzing the direct interaction between AT and hepatocytes, and reported that visceral adipose tissue (VAT) promotes lipid accumulation and apoptosis (lipotoxicity) in hepatocyte while subcutaneous adipose tissue (SAT) does not effect. VAT inducing phenomena are mediated by soluble factors. Recently, extracellular vesicles (EVs) including exosome receive attention as new players in metabolic organ cross-talk. Thus we hypothesized that EVs mediate the VAT-induced lipotoxicity in hepatocytes. Here we investigated the difference between EVs secreted by VAT and SAT. We revealed that VAT produces approximately 6 times more EVs than SAT. EVs purified from neither SAT nor VAT affected hepatocyte morphology.
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Academic Significance and Societal Importance of the Research Achievements |
脂肪組織から分泌されるEVsについて、VATとSATに相違があることを初めて明らかにした。VATとSATは起源が異なると考えられており、これを裏付ける研究成果であり、さらに、脂肪組織の部位による役割が異なることを示唆するものと考える。また、EVsにはmicroRNAが含まれており、脂肪組織は全身を循環するmicroRNAの最大の供給源との報告がある。癌でのmicroRNA研究は盛んであるが、代謝性疾患ではまだ不明な点が多い。本研究を発展させることで、種々の代謝性疾患等における病態制御に脂肪組織が果たす役割が解明される一助となると考える。
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