Abstract
BackgroundMetabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M1-like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has excellent anti-inflammatory activities and may be used in the treatment of a variety of inflammatory diseases. In this study, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice.MethodsNewborn mice were subcutaneously (s.c.) injected with monosodium glutamate (MSG) to establish a diabetes model. After 24 weeks, the MSG obese mice were divided into three groups and treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for 10 successive weeks, respectively.ResultsThe obesity model was successfully established, as the body weight, insulin resistance, fasting blood glucose (FBG) and dyslipidemia were significantly increased. The 10-week administration of piperine to the obese mice not only significantly decreased the elevated FBG (Model: 6.45 ± 0.41 mM; Piperine: 4.72 ± 0.44 mM, p < 0.01), serum TC (Model: 5.66 ± 0.66 mM; Piperine: 3.55 ± 0.30 mM, p < 0.01) and TG (Model: 1.41 ± 0.08 mM; Piperine: 0.94 ± 0.05 mM, p < 0.001), but also enhanced the glucose infusion rate in the hyperglycemic clamp experiment. Meanwhile, piperine improved glucose intolerance and insulin resistance in MSG obese mice. Piperine markedly decreased the total and differential white blood cell (WBC) count, the serum levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines such as galectin-3 (Gal-3) and interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M1-like polarization marker CD11c and Gal-3 in adipose tissues. The in vitro study showed that piperine inhibited LPS-stimulated polarization of RAW 264.7 cells toward the M1 phenotype.ConclusionsPiperine served as an immunomodulator for the treatment of obesity-related diabetes through its anti-inflammatory effects, which might be achieved by inhibiting macrophages M1 polarization in adipose tissues.
Highlights
Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance
Based on the body weight, Lee’s index, serum total cholesterol (TC), TG and fasting blood glucose (FBG), the 6-month-old monosodium glutamate (MSG) mice were divided into three groups: (i) the Model group, which was administered an equal volume of saline. (ii) the Piperine group and Metformin group, which were treated with 40 mg piperine/kg/day (Sigma-Aldrich, USA) and 150 mg metformin/kg/day (Sigma-Aldrich, USA) by gavage for 10 weeks, respectively
Effects of piperine on body weight, mesenteric fat accumulation, dietary intake and Lee’s index To explore the effect of piperine on the established obesity, body weight, mesenteric fat accumulation, Lee’s index, glycolipid metabolism and insulin sensitivity were assessed in the MSG-obese insulin resistant mice upon the piperine treatment
Summary
Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In addition to the classic pro-inflammatory cytokines mentioned above, Pingping Li et al found that the inflammatory mediator galectin-3 (gal-3), which is mainly secreted by M1-like macrophages in visceral adipose tissues, can inhibits the downstream signaling of the insulin receptor (IR) by directly binding with IR, leading to systemic insulin resistance [11,12,13]. These pieces of evidence indicate that modulation of the conversion of M1 to M2-like polarized state of macrophages, either by genetic or pharmacological methods, is a promising approach for the treatment of obesity-induced insulin resistance and diabetes
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