The mechanisms of carnosic acid attenuates tumor necrosis factor-α-mediated inflammation and insulin resistance in 3T3-L1 adipocytes




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).

Methods and 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 Tyr632 insulin receptor substrate-1 (IRS-1), Akt, and FoxO1, but decreased the TNF-α-induced phosphorylation of Ser307 IRS-1 and total FoxO1.


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.