Carbenoxolone ameliorates insulin sensitivity in obese mice induced by high fat diet via regulating the IκB-α/NF-κB pathway and NLRP3 inflammasome.
The characteristic feature of obesity and insulin resistance is chronic low-grade inflammation. Nod-Like Receptor Pyrin 3 (NLRP3) inflammasome plays a central role in obesity-induced insulin resistance. However, how does Carbenoxolone (CBX) play its role in ameliorating insulin resistance in peripheral tissues of obese mice induced by high-fat diet (HFD) remains unknown. In our study, we explored the molecular mechanism of CBX in improving insulin resistance in liver and skeletal muscle in mice induced by the HFD. Our results revealed that in the CBX group, a significant decrease in fasting blood glucose, insulin and HOMA-IR score were observed. CBX could attenuate intracellular lipid accumulation and inflammation aggravation in liver and skeletal muscle. Besides, treatment with CBX could significantly reduce expressions of p-IκB-α, p-NF-κB, p-IRS-1, NLRP3 and inflammatory factors, increase expressions of p-PI3K and p-AKT. Therefore, CBX could dramatically improve insulin resistance in liver and skeletal muscle in mice induced by the high-fat diet. In conclusions, we demonstrate that CBX has a significant protective effect on diet-induced obesity in mice. The potential mechanisms include inhibiting IκB-α/NF-κB pathway, restricting the production of NLRP3 inflammasome and other inflammatory factors, reducing the expression of p-IRS-1, increasing the expressions of p-PI3K and p-AKT, thus ameliorating insulin resistance in liver and skeletal muscle of high-fat diet mice. Therefore CBX is an active agent against diet-induced obesity and is given the opportunity for the treatment of obesity related diseases.
['Chen|Yuning|Y|', 'Qian|Qian|Q|', 'Yu|Jian|J|']
D000818:Animals D002229:Carbenoxolone D059305:Diet, High-Fat D005786:Gene Expression Regulation D007249:Inflammation D007333:Insulin Resistance D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D018482:Muscle, Skeletal D000072000:NF-KappaB Inhibitor alpha D016328:NF-kappa B D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D009765:Obesity D011897:Random Allocation
Carbenoxolone Obesity IκB-α/NF-κB pathway NLRP3 inflammasome Insulin resistance