Resveratrol prevents hepatic steatosis and endoplasmic reticulum stress and regulates the expression of genes involved in lipid metabolism, insulin resistance, and inflammation in rats.

Previous research demonstrated that resveratrol possesses promising properties for preventing obesity. Endoplasmic reticulum (ER) stress was proposed to be involved in the pathophysiology of both obesity and hepatic steatosis. In the current study, we hypothesized that resveratrol could protect against high-fat diet (HFD)-induced hepatic steatosis and ER stress and regulate the expression of genes related to hepatic steatosis. Rats were fed either a control diet or a HFD for 12 weeks. After 4 weeks, HFD-fed rats were treated with either resveratrol or vehicle for 8 weeks. Body weight, serum metabolic parameters, hepatic histopathology, and hepatic ER stress markers were evaluated. Moreover, an RT2 Profiler Fatty Liver PCR Array was performed to investigate the mRNA expressions of 84 genes related to hepatic steatosis. Our work showed that resveratrol prevented dyslipidemia and hepatic steatosis induced by HFD. Resveratrol significantly decreased activating transcription factor 4, C/EBP-homologous protein and immunoglobulin binding protein levels, which were elevated by the HFD. Resveratrol also decreased PKR-like ER kinase phosphorylation, although it was not affected by the HFD. Furthermore, resveratrol increased the expression of peroxisome proliferator-activated receptor δ, while decreasing the expression of ATP citrate lyase, suppressor of cytokine signaling-3, and interleukin-1ß. Our data suggest that resveratrol can prevent hepatic ER stress and regulate the expression of peroxisome proliferator-activated receptor δ, ATP citrate lyase, suppressor of cytokine signaling-3, tumor necrosis factor α, and interleukin-1ß in diet-induced obese rats, and these effects likely contribute to resveratrol's protective function against excessive accumulation of fat in the liver.

Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet.

Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.