title: The mechanisms of carnosic acid attenuates tumor necrosis factor-α-mediated inflammation and insulin resistance in 3T3-L1 adipocytes.
abstract: METHODS
  Insulin resistance has been linked to a low-grade chronic inflammatory response. Carnosic acid (CA), which is found in rosemary, has been reported to have antioxidant, anti-inflammation, and anti-adipogenic properties. Here, we examined the effects of CA on inflammation and insulin resistance in 3T3-L1 adipocytes treated with tumor necrosis factor-α (TNF-α).
  
  
  RESULTS
  CA attenuated the TNF-α-induced mRNA expression of inflammatory genes, including IL-6 and monocyte chemoattractant protein-1. CA also attenuated the TNF-α-mediated activation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and c-Jun; the phosphorylation of inhibitor-κB (IκB) kinase (IKK)α/β, the phosphorylation and degradation of IκBα, the nuclear translocation of p65, and the DNA-binding activity of NF-κB and AP-1. CA or PP242 (an mTOR inhibitor) suppressed the TNF-α-induced protein expression of mTOR, p70S6K, eIF4E, and IL-6. Moreover, CA attenuated the TNF-α-mediated suppression of peroxisome proliferator-activated receptor γ, adiponectin, and adipocyte protein 2. CA reversed the TNF-α-mediated suppression of insulin-stimulated glucose uptake and the phosphorylation of Tyr(632) insulin receptor substrate-1 (IRS-1), Akt, and FoxO1, but decreased the TNF-α-induced phosphorylation of Ser(307) IRS-1 and total FoxO1.
  
  
  CONCLUSIONS
  CA attenuates TNF-α-mediated inflammation via inhibition of NF-κB and AP-1 pathways and insulin resistance via Akt-dependent FoxO1 signaling in 3T3-L1 adipocytes.
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.forename: Kai-Li
authors.initials: KL
authors.lastname: Liu
authors.forename: Yu-Ru
authors.initials: YR
authors.lastname: Lin
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Kuo
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects; D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D045784:Abietanes; D007328:Insulin; D016328:NF-kappa B; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C546843:mTOR protein, mouse; C018381:salvin
keywords: 3T3-L1 adipocytes; Carnosic acid; Inflammation; Insulin resistance; Tumor necrosis factor-α