title: (-)-Epicatechin prevents TNFα-induced activation of signaling cascades involved in inflammation and insulin sensitivity in 3T3-L1 adipocytes.
abstract: Obesity is major public health concern worldwide and obese individuals exhibit a higher risk of chronic diseases such as type 2 diabetes. Inflammation plays a significant role in metabolic regulation and mounting evidence highlight the contribution of adipose tissue to systemic inflammatory state. Food extracts with a high content of (-)-epicatechin have been found to exert systemic anti-inflammatory actions, however the anti-inflammatory actions of (-)-epicatechin on adipose tissue remain to be determined. The aim of this study was to investigate the capacity of (-)-epicatechin to prevent tumor necrosis alpha (TNFα)-induced activation of cell signals involved in inflammation and insulin resistance (NF-κB, mitogen-activated protein kinases (MAPKs), AP-1, and peroxisome proliferator activated receptor γ (PPARγ)) in differentiated white adipocytes (3T3-L1). TNFα triggered the activation of transcription factors NF-κB and AP-1, and MAPKs ERK1/2, JNK, and p38. (-)-Epicatechin caused a dose (0.5-10 μM)-dependent decrease in TNFα-mediated JNK, ERK1/2, and p-38 phosphorylation, and nuclear AP-1-DNA binding. (-)-Epicatechin also inhibited TNFα-triggered activation of the NF-κB signaling cascade, preventing TNFα-mediated p65 nuclear transport and nuclear NF-κB-DNA binding. (-)-Epicatechin also attenuated the TNFα-mediated downregulation of PPARγ expression and decreased nuclear DNA binding. Accordingly, (-)-epicatechin inhibited TNFα-mediated altered transcription of genes (MCP-1, interleukin-6, TNFα, resistin, and protein-tyrosine phosphatase 1B) involved in inflammation and insulin signaling. In conclusion, (-)-epicatechin can attenuate TNFα-mediated triggering of signaling cascades involved in inflammation and insulin resistance. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.
authors.affiliation: Department of Pathology, School of Medicine, National University of Cuyo, Argentina.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Vazquez-Prieto
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bettaieb
authors.forename: Fawaz G
authors.initials: FG
authors.lastname: Haj
authors.forename: César G
authors.initials: CG
authors.lastname: Fraga
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Oteiza
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; D020928:Mitogen-Activated Protein Kinases