Anti-inflammatory effect of piperine ameliorates insulin resistance in monosodium glutamate–treated obese mice

Abstract

Background : Metabolic inflammation has been considered as an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M 1 -like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has been proven to have excellent anti-inflammatory activity and has therapeutic effects on a variety of inflammatory diseases. Therefore, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods: In this study, the monosodium glutamate (MSG) obese mice model was used. The 6-month-old MSG mice were divided into three groups, which were treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for successive 10 weeks, respectively. Meanwhile, the 6-month-old normal mice without MSG treatment were selected as normal controls. Results: When the obesity model was successfully established, obesity degree, insulin resistance, fasting blood glucose(FBG) and serum lipid profiles were significantly increased. Our results showed that the 10-week administration of piperine (40 mg/kg/d) not only significantly decreased the elevated FBG, serum TC and TG levels, but also enhanced infusion rate in hyperglycemic clamp experiment and improved the oral glucose intolerance as well as abnormal insulin tolerance in adult MSG obese mice. Additionally, piperine significantly decreased the total and differential white blood cell (WBC) count and the serum level of lipopolysaccharide (LPS), pro-inflammatory cytokines such as galectin-3 (Gal-3), interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M 1 -like polarization marker CD11c and Gal-3 in adipose tissues. In addition, the in vitro study showed that piperine inhibited LPS- stimulated polarization of RAW 264.7 cells toward the M 1 phenotype. Conclusions: In summary, these findings demonstrated that piperine could significantly inhibit body weight gain, reduce fat accumulation, rectify glycolipid metabolism disorders, improve severe insulin resistance and ameliorates systemic metabolic inflammation in MSG obesity mice. Our study indicates that piperine, as a potential natural alkaloid, can be used in the treatment of obesity-associated diabetes by delaying the progression of obesity-induced insulin resistance.