title: Grape powder extract attenuates tumor necrosis factor α-mediated inflammation and insulin resistance in primary cultures of human adipocytes.
abstract: Grapes are rich in phenolic phytochemicals that possess anti-oxidant and anti-inflammatory properties. However, the ability of grape powder extract (GPE) to prevent inflammation and insulin resistance in human adipocytes caused by tumor necrosis factor α (TNFα), a cytokine elevated in plasma and white adipose tissue (WAT) of obese, diabetic individuals, is unknown. Therefore, we examined the effects of GPE on markers of inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes treated with TNFα. We found that GPE attenuated TNFα-induced expression of inflammatory genes including interleukin (IL)-6, IL-1β, IL-8, monocyte chemoattractant protein (MCP)-1, cyclooxygenase (COX)-2 and Toll-like receptor (TLR)-2. GPE attenuated TNFα-mediated activation of extracellular signal-related kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) and activator protein-1 (AP-1, i.e., c-Jun). GPE also attenuated TNFα-mediated IκBα degradation and nuclear factor-kappa B (NF-κB) activity. Finally, GPE prevented TNFα-induced expression of protein tyrosine phosphatase (PTP)-1B and phosphorylation of serine residue 307 of insulin receptor substrate-1 (IRS-1), which are negative regulators of insulin sensitivity, and suppression of insulin-stimulated glucose uptake. Taken together, these data demonstrate that GPE attenuates TNFα-mediated inflammation and insulin resistance in human adipocytes, possibly by suppressing the activation of ERK, JNK, c-Jun and NF-κB.
authors.affiliation: Department of Nutrition, University of North Carolina-Greensboro, Greensboro, NC 27402, USA.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Chuang
authors.forename: Akkarach
authors.initials: A
authors.lastname: Bumrungpert
authors.forename: Arion
authors.initials: A
authors.lastname: Kennedy
authors.forename: Angel
authors.initials: A
authors.lastname: Overman
authors.forename: Tiffany
authors.initials: T
authors.lastname: West
authors.forename: Brent
authors.initials: B
authors.lastname: Dawson
authors.forename: Michael K
authors.initials: MK
authors.lastname: McIntosh
mesh_terms: D050153:Abdominal Fat / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019440:Anti-Obesity Agents / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005638:Fruit / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D027843:Vitis / Q000737:chemistry*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; C526292:IRS1 protein, human; D018836:Inflammation Mediators; D055504:Insulin Receptor Substrate Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1