Molecules and Cells

  • 제45권9호
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  • Pages.649-659
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Lysosome Inhibition Reduces Basal and Nutrient-Induced Fat Accumulation in Caenorhabditis elegans

  • Lu, Rui (School of Food and Biological Engineering, Hefei University of Technology) ;
  • Chen, Juan (School of Food and Biological Engineering, Hefei University of Technology) ;
  • Wang, Fangbin (School of Food and Biological Engineering, Hefei University of Technology) ;
  • Wang, Lu (School of Food and Biological Engineering, Hefei University of Technology) ;
  • Liu, Jian (School of Food and Biological Engineering, Hefei University of Technology) ;
  • Lin, Yan (School of Food and Biological Engineering, Hefei University of Technology)
  • 투고 : 2021.09.09
  • 심사 : 2022.05.02
  • 발행 : 2022.09.30
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초록

A long-term energy nutritional imbalance fundamentally causes the development of obesity and associated fat accumulation. Lysosomes, as nutrient-sensing and lipophagy centers, critically control cellular lipid catabolism in response to nutrient deprivation. However, whether lysosome activity is directly involved in nutrient-induced fat accumulation remains unclear. In this study, worm fat accumulation was induced by 1 mM glucose or 0.02 mM palmitic acid supplementation. Along with the elevation of fat accumulation, lysosomal number and acidification were also increased, suggesting that lysosome activity might be correlated with nutrient-induced fat deposition in Caenorhabditis elegans. Furthermore, treatments with the lysosomal inhibitors chloroquine and leupeptin significantly reduced basal and nutrient-induced fat accumulation in C. elegans. The knockdown of hlh-30, which is a critical gene in lysosomal biogenesis, also resulted in worm fat loss. Finally, the mutation of aak-2, daf-15, and rsks-1 showed that mTORC1 (mechanistic target of rapamycin complex-1) signaling mediated the effects of lysosomes on basal and nutrient-induced fat accumulation in C. elegans. Overall, this study reveals the previously undescribed role of lysosomes in overnutrition sensing, suggesting a new strategy for controlling body fat accumulation.

키워드

과제정보

We thank Professor Liu, Pingsheng (State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences) for providing the LIU1 strain and Professor Xiaochen Wang (National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences) for providing qxIs750. This work was supported by the National Natural Science Foundation of China (32070757 to J.L.), the Industrial Innovation Funds for Linquan County-Hefei University of Technology (JZ2018QTXM0553 to J.L.), and the University Synergy Innovation Program of Anhui Province (GXXT-2019-026 to J.L.). Some C. elegans strains were provided by the CGC, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440).

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