Acute exposure to resveratrol inhibits AMPK activity in human skeletal muscle cells
ABSTRACT Recent studies have suggested resveratrol (RSV) as a new natural therapeutic agent to treat type 2 diabetes and lipid-induced insulin resistance. Here, we investigated whether RSV could reverse palmitate-induced insulin resistance in human primary muscle cells.
Myotubes obtained from six healthy men (54 ± 3 years (mean ± SE), BMI 25.0 ± 1.7 kg/m(2), fasting plasma glucose concentration (fP-glucose) 5.47 ± 0.09 mmol/l) were treated for 4 h with 100 μmol/l RSV and/or 0.2 mmol/l palmitate, and stimulated with or without 100 nmol/l insulin. Assays of glucose uptake, glycogen synthesis, palmitate oxidation, intracellular signalling and AMP-activated protein kinase (AMPK) activity were performed.
RSV did not reverse palmitate-induced impairment of glucose metabolism. Surprisingly, RSV decreased glucose uptake and glycogen synthesis in human skeletal muscle cells. Palmitate oxidation and phosphorylation of AMPK and its downstream target acetyl-CoA carboxylase β (ACCβ) were inhibited by RSV, and RSV completely blocked the activity of AMPK isoform complexes α1/β2/γ1 and α2/β2/γ1 in in-vitro kinase activity assays. Endoplasmic reticulum (ER) stress was increased in response to RSV, as indicated by increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) and increased expression of CCAAT/enhancer binding protein homologous protein (CHOP).
Acute exposure to RSV inhibits AMPK activity, fatty-acid oxidation and glucose metabolism in human myotubes.
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ABSTRACT: For several decades, there has been increasing interest in the possible use of resveratrol as a preventative agent in cardiovascular disease. Resveratrol exerts numerous effects on adipocyte, hepatocyte, and endothelial cell development and function. Many investigations have demonstrated the ability of resveratrol to regulate the adipocyte lifecycle, lipid synthesis, and improve hepatic lipid metabolism. Resveratrol has numerous vascular protective effects on endothelial tissue, including its antiplatelet activity. Resveratrol also reduces intracellular oxidative stress. Animal models of obesity and cardiovascular diseases have yielded important contributions to our understanding of the effects of resveratrol on the vasculature and the risk for pathology. In limited human studies, resveratrol reduces the release of proinflammatory cytokines and improves systemic glucose and insulin regulation and decreases cellular oxidative stress. Therefore, resveratrol has significant potential as both a prophylactic and treatment agent. However additional studies are required to more completely characterize its impacts on human physiology and its benefits in the setting of disease.Current Cardiovascular Risk Reports 02/2013; 7(1). DOI:10.1007/s12170-012-0289-2
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ABSTRACT: Qushi Huayu Decoction (QHD), a Chinese herbal formula, has been proven effective on alleviating nonalcoholic fatty liver disease (NAFLD) in human and rats. The present study was conducted to investigate whether QHD could inhibit hepatic lipid accumulation by activating AMP-activated protein kinase (AMPK) in vivo and in vitro. Nonalcoholic fatty liver (NAFL) model was duplicated with high-fat diet in rats and with free fatty acid (FFA) in L02 cells. In in vivo experimental condition, QHD significantly decreased the accumulation of fatty droplets in livers, lowered low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in serum. Moreover, QHD supplementation reversed the HFD-induced decrease in the phosphorylation levels of AMPK and acetyl-CoA carboxylase (ACC) and decreased hepatic nuclear protein expression of sterol regulatory element-binding protein-1 (SREBP-1) and carbohydrate-responsive element-binding protein (ChREBP) in the liver. In in vitro, QHD-containing serum decreased the cellular TG content and alleviated the accumulation of fatty droplets in L02 cells. QHD supplementation reversed the FFA-induced decrease in the phosphorylation levels of AMPK and ACC and decreased the hepatic nuclear protein expression of SREBP-1 and ChREBP. Overall results suggest that QHD has significant effect on inhibiting hepatic lipid accumulation via AMPK pathway in vivo and in vitro.Evidence-based Complementary and Alternative Medicine 03/2013; 2013:184358. DOI:10.1155/2013/184358 · 1.88 Impact Factor
- Cell Death & Disease 06/2013; 4(6):e680. DOI:10.1038/cddis.2013.196 · 5.01 Impact Factor