2021 Fiscal Year Final Research Report
Elucidation of the mechanism by which autophagy regulates energy metabolism in multilocular adipocytes.
Project/Area Number |
19K09025
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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Research Institution | Kobe University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 褐色脂肪細胞 |
Outline of Final Research Achievements |
In this study, we investigated autophagy, lipolysis, and energy metabolism in brown adipocytes. In cultured 3T3-L1 adipocytes with multilocular lipid droplets, autophagy was enhanced by serum removal and the intracellular triglyceride content was reduced, but the reduction in triglyceride content was suppressed by treatment with chloroquine, an autophagy inhibitor. In brown adipocytes of FSP27β-deficient mice, multilocular lipid droplets were changed to monolocular lipid droplet formation. In addition, fasting-induced autophagy and the following decrease of intracellular lipid mass were suppressed in brown adipocytes of these mice. However, respiratory quotient was increased in the respiratory metabolism of FSP27β-deficient mice, indicating the decreased lipid utilization. It was suggested that in brown adipocytes, multilocular lipid droplet formation is involved in the enhancement of autophagy, and may affect systemic energy metabolism by regulating lipolysis induced by autophagy.
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Free Research Field |
糖尿病代謝
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Academic Significance and Societal Importance of the Research Achievements |
脂肪細胞ではリパーゼ以外による脂肪分解経路については検討がほとんどなされていなかった。さらに細胞内脂肪滴形態とエネルギー代謝の関連を検討した研究もほぼ皆無であった。褐色脂肪細胞は細胞内で脂肪酸を酸化してエネルギーを産生する細胞である事を考えると、多房性脂肪滴という特徴的形態がオートファジーを活性化し、リポファジーによる脂肪分解がリパーゼによる脂肪分解に追加され、脂質を基質としたエネルギー産生を亢進させることが示唆された事は興味深い。また褐色脂肪細胞にオートファジーを誘導できれば、全身のエネルギー代謝にも影響を及ぼす可能性があり肥満治療を見据えても意義深い。
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