| First Author | Xue W | Year | 2020 |
| Journal | Eur J Pharmacol | Volume | 871 |
| Pages | 172910 | PubMed ID | 31926991 |
| Mgi Jnum | J:297843 | Mgi Id | MGI:6479325 |
| Doi | 10.1016/j.ejphar.2020.172910 | Citation | Xue W, et al. (2020) Caveolin-1 alleviates lipid accumulation in NAFLD associated with promoting autophagy by inhibiting the Akt/mTOR pathway. Eur J Pharmacol 871:172910 |
| abstractText | Non-alcoholic fatty liver disease (NAFLD) is the most burgeoning chronic liver disease worldwide whose pathogenesis is complex and controversial. Here, we investigated the impact of caveolin-1 (CAV1), a scaffolding protein of caveolae for lipid homeostasis and endocytosis, on the pathogenesis of NAFLD. CAV1 and caveolae play crucial roles in the regulation of autophagy and hepatic energy metabolism. However, it remains unclear whether CAV1 could affect hepatic lipid metabolism by regulating autophagy. In this study, results showed that the expressions of CAV1 and autophagy-related proteins (Beclin1 and LC3-II/) were decreased, while the level of p62 was increased in HFD (high-fat diet) fed mice liver and in A/O (alcohol and oleic acid mixture) treated L02 cells, compared to the corresponding controls. In vivo study, upregulation of CAV1 with CAV1 scaffolding domain peptides (CSD, amino acids 82-101 of caveolin-1) could alleviate lipid accumulation and promote autophagy in NAFLD mice. In vitro study, CAV1 overexpression plasmid and its small interfering RNA were cultured with A/O treated L02 cells respectively. The results also demonstrated that CAV1 reduced lipid accumulation and promoted autophagy in L02 cells. Treatment with chloroquine, an inhibitor of autophagic degradation, abrogated CAV1 plasmid-mediated alleviation of lipid accumulation. Mechanistically, the inhibition of Akt/mTOR pathway was involved in the protective role of CAV1 in autophagy induction and lipid metabolism in NAFLD. Together, these results provided novel perception into the function of CAV1 in liver through autophagy and emphasized its positive role in NAFLD. |
