Adenovirus-mediated liver-specific expression of SIRT1 or a phosphor-defective S164A-SIRT1 mutant promoted fatty acid oxidation and ameliorated liver steatosis and glucose intolerance in diet-induced obese mice, but these beneficial effects were not observed in mice expressing a phosphor-mimic S164D-SIRT1 mutant.
These studies indicate that SIRT1 serves as a negative regulator of UPR signaling in T2DM and that SIRT1 attenuates hepatic steatosis, ameliorates insulin resistance, and restores glucose homeostasis, largely through the inhibition of mTORC1 and ER stress.
Activating AMPK<i>α</i> negatively regulates Egr1 to inhibit inflammatory cytokines in high glucose. miR-34a inhibition increases phosphorylated AMPK<i>α</i> through mediating SIRT1 to suppress the development of fatty liver.
Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance.
We are the first to demonstrate that the SIRT1/HMGB1 pathway is a key therapeutic target for controlling NAFLD inflammation and that SalB confers protection against HFD- and PA-induced hepatic steatosis and inflammation through SIRT1-mediated HMGB1 deacetylation.
Epigallocatechin-3-Gallate-Rich Green Tea Extract Ameliorates Fatty Liver and Weight Gain in Mice Fed a High Fat Diet by Activating the Sirtuin 1 and AMP Activating Protein Kinase Pathway.
To model human fatty livers, we repopulated decellularized rat livers with human mesenchymal cells, fibroblasts, macrophages, and human SIRT1 knockdown iPSC-derived hepatocytes and found that the human iPSC-derived liver tissue developed macrosteatosis, acquired proinflammatory phenotype, and shared a similar lipid and metabolic profiling to human fatty livers.
SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, controlling hepatic oxidative stress and mediating hepatic inflammation through deacetylating some transcriptional regulators against the progression of fatty liver diseases.
The SIRT1/heat shock factor 1/HSP pathway is essential for exenatide-alleviated, lipid-induced ER stress and hepatic steatosis, which provides evidence for a molecular mechanism to support exenatide and incretin mimetics as promising therapeutics for obesity-induced hepatic steatosis.(Hepatology 2017;66:809-824).
Massive studies have suggested that liver steatosis is closely associated with the inhibition of silent information regulator 1 (SIRT1) and the augment of lipin1 β/α ratio mediated by ethanol.
Therefore, we investigated whether the beneficial effects of exendin-4 treatment on fatty liver are mediated via Sirt1 in high-fat (HF) diet-induced obese C57BL/6J mice and related cell culture models.
The present study demonstrated that SIRT1 activation attenuated HFD‑induced liver steatosis and inflammation by inhibiting CD36 expression and the NF‑κB signaling pathway.
The results revealed that the SIRT1/AMPK pathway is involved in the functions of the three flavonones, and the most effective flavonone against hepatic steatosis might be PCBG, followed by MPG and PCB.