School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
Engineering Research Center of Bioprocess, Ministry of Education, Hefei University of Technology, Hefei 230009, China.
Mol Cells. 2022 Sep 30;45(9):649-659. doi: 10.14348/molcells.2022.0073. Epub 2022 Aug 29.
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 . Furthermore, treatments with the lysosomal inhibitors chloroquine and leupeptin significantly reduced basal and nutrient-induced fat accumulation in . The knockdown of , which is a critical gene in lysosomal biogenesis, also resulted in worm fat loss. Finally, the mutation of , , and showed that mTORC1 (mechanistic target of rapamycin complex-1) signaling mediated the effects of lysosomes on basal and nutrient-induced fat accumulation in . Overall, this study reveals the previously undescribed role of lysosomes in overnutrition sensing, suggesting a new strategy for controlling body fat accumulation.
长期的能量营养失衡从根本上导致肥胖和相关脂肪堆积的发展。溶酶体作为营养感应和脂自噬中心，在营养缺乏时，能严格控制细胞脂质分解代谢。然而，溶酶体活性是否直接参与营养诱导的脂肪积累仍不清楚。在这项研究中，通过补充 1mM 葡萄糖或 0.02mM 棕榈酸诱导线虫脂肪积累。随着脂肪积累的增加，溶酶体数量和酸化也增加，这表明溶酶体活性可能与营养诱导的脂肪沉积有关。此外，用溶酶体抑制剂氯喹和亮抑蛋白酶肽处理也显著减少线虫的基础和营养诱导的脂肪积累。溶酶体生物发生的关键基因 的敲低也导致线虫脂肪损失。最后， 的突变体 、 和 表明 mTORC1（雷帕霉素复合物 1 的机械靶标）信号转导介导了溶酶体对基础和营养诱导的脂肪积累的影响。总的来说，这项研究揭示了溶酶体在营养过剩感应中的先前未描述的作用，为控制体脂积累提供了一种新策略。
