<p>Resveratrol reduces liver endoplasmic reticulum stress and improves insulin sensitivity in vivo and in vitro</p>

Abstract

Purpose : The aim of the study was to examine the effects of resveratrol upon hepatic endoplasmic reticulum stress (ERS) and insulin sensitivity in vivo and in vitro. Material and methods : C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, and insulin resistance was evaluated by the intraperitoneal glucose tolerance test (IPGTT). Mice were then treated with resveratrol for 12 weeks and blood and liver samples collected. Blood biochemical indicators were determined by kits, liver protein expression was determined by western blot, and morphological changes were observed by histological staining. Palmitic acid (PA)-induced insulin-resistant HepG2 cells were established. Cells were exposed to 100, 50 or 20 μM resveratrol for 24 hrs, and proliferation/cytotoxicity was determined. Cells were divided into five groups: control, PA, PA + Rev (100 μM), PA + Rev (50 μM) and PA + Rev (20 μM) groups. After 24 hrs of treatment, cellular proteins were analyzed the same way as animal tissues. Results : The IPGTT confirmed that the insulin resistance model was established successfully. After resveratrol treatment, fasting blood glucose and cholesterol levels declined and the quantitative insulin sensitivity check index increased. Western-blot results showed that resveratrol-treated HFD mice had reduced hepatic levels of p-PERK, ATF-4 and TRIB3, and increased the levels of ATF-6, p-AKT and p-GSK3β. In the cell model, resveratrol with 100 and 50 μM enhanced ERS and insulin resistance, whereas 20 μM had beneficial effects, similar to the animal model. Conclusion : Resveratrol reduced hepatic ERS, thereby improving insulin sensitivity and glucose levels. However, high doses of resveratrol had harmful effects on cells, elevating ERS and insulin resistance. The safe dose of resveratrol needs further investigation.

Sex Hormone Binding Globulin (SHBG) Mitigates ER Stress in Hepatocytes In Vitro and Ex Vivo

“…The accumulation of FFA and in particular overload with saturated fatty acids (SFA) trigger lipotoxicicty, lipoapoptosis, and finally IR development in the liver [ 11 , 12 ]. As a consequence, fatty degeneration in hepatocytes and increased levels of C-reactive protein (CRP) in circulating blood initiate the development of endoplasmic reticulum stress (ER stress) [ 13 ].…”

Resveratrol Metabolites Are Able to Reduce Steatosis in Cultured Hepatocytes

“…When higher concentrations were used, only 10 µM DH-R and 25 µM R-4G induced significant effects. However, several authors have reported positive effects of resveratrol at higher concentrations (10–100 µM) in in vitro assays [ 46 , 47 ]. Indeed, Ji et al (2015) reported a reduction in triglyceride levels in AML12 cells from 25 to 100 μM of resveratrol.…”

Resveratrol Modulates the Gut-Brain Axis: Focus on Glucagon-Like Peptide-1, 5-HT, and Gut Microbiota

“…Resveratrol could boost glucose uptake in the absence of insulin (Zhao et al, 2019). It also exerts an anti-diabetic property via enhancing mitochondrial function and an anti-aging property via promoting energy expenditure (Ren et al, 2017;Zou et al, 2017).…”