Resveratrol reduces high glucose-induced de-novo lipogenesis through mTOR mediated induction of autophagy in HepG2 cells
Abstract
Resveratrol has been reported to decrease lipid accumulation in the liver, but the molecular mechanism underlying this effect remains unknown. In this study, the role of autophagy in high glucose (HG)-induced lipogenesis in the presence of resveratrol in HepG2 cells was investigated. Resveratrol pretreatment prevented HG-induced total lipid content, triglyceride level, apo B secretion, and key lipogenic gene expression (FAS, ACC, SREBP1c, and MTP). HG diminished p-Foxo1 and p-AMPK levels, while resveratrol reversed this effect by inducing p-Foxo1 and p-AMPK levels by 40% and 47%, respectively. HG treatment reduced autophagy markers such as LC3-II, ATG5, and ATG7 and increased p62 protein levels, whereas resveratrol significantly reversed these effects. Additionally, inhibiting autophagy with chloroquine led to enhanced total lipid and triglyceride content compared to untreated control cells. Notably, co-treatment with chloroquine inhibited the preventive effect of resveratrol on HG-induced lipogenesis in HepG2 cells. Furthermore, while HG induced p-mTOR level in HepG2 cells, resveratrol reversed this effect. Rapamycin, an inhibitor of mTOR, ameliorated HG-induced total lipid and triglyceride content and the expression of lipogenic genes. Collectively, these data demonstrate that the lipid-lowering effect of resveratrol is mediated through the induction of autophagy in an mTOR-dependent mechanism.
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| Files | ||
| Issue | Vol 1 No 1 (2023) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/abi.v1i1.14063 | |
| Keywords | ||
| High Glucose lipogenesis Resveratrol autophagy Liver HepG2 lipid accumulation mTOR | ||
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