Resveratrol modulates adipokine expression and improves insulin sensitivity in adipocytes: Relative to inhibition of inflammatory responses.
Resveratrol is a potent inhibitor of inflammation and has anti-diabetic potentiality, however whether its anti-inflammatory potency contributes to the amelioration of diabetes or insulin resistance remains to be determined. This study aims at evaluating the effects of resveratrol on inflammation-related adipokines expression and insulin sensitivity in adipocytes. We stimulated RAW264.7 cells with LPS and collected the supernatant as a conditioned medium (CM) for the culture of adipocytes. Resveratrol, at concentrations ranging from 0.1 to 10 muM, effectively inhibited lipopolysaccharide (LPS)-induced TNF-alpha and IL-6 production with the downregulation of relative genes expression in macrophages. Exposing differentiated 3T3-L1 cells to RAW264.7 CM resulted in gene over-expressions of TNF-alpha, IL-6 and resistin, however, mRNA expression of adiponectin and PPARgamma were down-regulated. Pretreatment of CM from resveratrol-treated macrophages reduced the elevated levels of TNF-alpha and IL-6, and significantly reversed inflammation-related changes in adipokine gene expression in 3T3-L1 adipocytes. Resveratrol suppressed extracellular receptor-activated kinase (ERK) and transcription factor-kappaB (NF-kappaB) activation by reducing the phosphorylation of ERK1/2 and NF-kappaB p65; moreover, it modulated insulin signaling transduction by modification of Ser/Thr phosphorylation of insulin receptor substrate-1 (IRS-1) and downstream AKT (T308), and thereby improved insulin sensitivity in adiposities. These results demonstrated that resveratrol modulated adipokines expression and improved insulin sensitivity which relative to inhibition of inflammatory-like response in adipocytes.
Kang
Liu
L
Department of Pharmacology for Chinese Materia Medica, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, China.
Heng
Wang
W
Yuan
An
A
Baolin
Liu
L
Fang
Huang
H
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D054392:Adipokines / Q000235:genetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D054392:Adipokines; D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D007328:Insulin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose; D000077185:Resveratrol