Lu Jing, Zhou Hongjiang, Hu Jinping, Zhang Ranran, Meng Zhuoqun, Guan Shuang
Department of Food Quality and Safety, College of Food Science and Engineering, Jilin University, Changchun, Jilin 130062, P. R. China.
College of Animal Science, Jilin University, Changchun, Jilin 130062, P. R. China.
J Agric Food Chem. 2024 Dec 18;72(50):27965-27977. doi: 10.1021/acs.jafc.4c08430. Epub 2024 Dec 4.
Apigenin (4',5,7-trihydroxyflavone) is a significant natural flavonoid compound that is abundantly found in various fruits and vegetables. It has been demonstrated to alleviate nonalcoholic fatty liver disease and exhibit lipid-lowering effects. However, its impact on lipid droplet (LD) degradation in hepatocytes remains unclear. LDs, coated by perilipins (PLINs), are selectively exposed and degraded through chaperone-mediated autophagy (CMA), specifically targeting PLIN2 and PLIN3 to enhance lipolysis and lipophagy. Lysosome-associated membrane protein type 2A (LAMP-2A) is the rate-limiting component of CMA. We found that apigenin-alleviated high-fat diet induced LD accumulation in hepatocytes by promoting CMA. The data indicated that apigenin could improve the expression of LAMP-2A, while downregulating the expression of PLIN2 and PLIN3, reduce the volume and size of LDs. AMP-activated protein kinase (AMPK) plays a crucial role in activating nuclear factor erythroid 2-related factor 2 (Nrf2), in turn, regulating the transcription of LAMP-2A. In our study, we found that the activation of AMPK induced by apigenin promotes PLIN2 phosphorylation and Nrf2 nuclear translocation, thus subsequently enhancing the activity of CMA. This accelerated the degradation of PLINs, ultimately facilitating LD degradation. Overall, our study offered valuable insights into the mechanism of apigenin in the degradation of LDs.
芹菜素（4'，5，7-三羟基黄酮）是一种重要的天然黄酮类化合物，在各种水果和蔬菜中大量存在。已证明它可减轻非酒精性脂肪性肝病并具有降脂作用。然而，其对肝细胞中脂滴（LD）降解的影响仍不清楚。由外周蛋白（PLINs）包被的脂滴通过伴侣介导的自噬（CMA）被选择性地暴露和降解，特别是靶向PLIN2和PLIN3以增强脂肪分解和脂质自噬。溶酶体相关膜蛋白2A型（LAMP-2A）是CMA的限速成分。我们发现芹菜素通过促进CMA减轻高脂饮食诱导的肝细胞中脂滴积累。数据表明，芹菜素可提高LAMP-2A的表达，同时下调PLIN2和PLIN3的表达，减小脂滴的体积和大小。腺苷酸活化蛋白激酶（AMPK）在激活核因子红细胞2相关因子2（Nrf2）中起关键作用，进而调节LAMP-2A的转录。在我们的研究中，我们发现芹菜素诱导的AMPK激活促进PLIN2磷酸化和Nrf2核转位，从而随后增强CMA的活性。这加速了PLINs的降解，最终促进了脂滴的降解。总体而言，我们的研究为芹菜素在脂滴降解中的机制提供了有价值的见解。
