Combination treatment with quercetin and resveratrol attenuates high fat diet-induced obesity and associated inflammation in rats via the AMPKα1/SIRT1 signaling pathway

Abstract

Diet-induced obesity is associated with systemic inflammation, which is considered to originate predominantly from the adipose tissue. Quercetin and resveratrol are two dietary polyphenols that exhibit anti-inflammatory properties and anti-insulin resistance when administered in isolation or combination (CQR). It remains unknown whether CQR reduces high fat diet (HFD)-induced obesity and inflammation in rats. In the current study, 46 male Wistar rats were divided into two groups, one of which was fed a normal diet (ND, 5.4% fat, w/w) and one of which was fed a HFD (45% fat, w/w) for 3 weeks. Following removal of the 12 most obesity-resistant rats from the HFD group, the remaining rats were divided into two sub-groups: A HFD group and a HFD+CQR group (administered 120 mg/kg/day resveratrol and 240 mg/kg/day quercetin). The results revealed that the HFD+CQR group had significantly lower body weights at 11 weeks compared with the HFD group and had significantly reduced visceral adipose tissue weights and adipocyte sizes. Serum lipid profiles were also significantly ameliorated in the HFD+CQR group. CQR attenuated the expression of systemic proinflammatory adipokines, including leptin, tumor necrosis factor-α, monocyte chemoattractant protein-1 and interleukin-6. It also reduced the recruitment of mast cells to the epididyotic adipose tissue (EAT). Furthermore, CQR reversed the HFD-induced suppression of 5'-adenosine monophosphate-activated protein kinase α1 (AMPKα1) phosphorylation and sirtuin 1 (SIRT1) expression in EAT. In conclusion, CQR may suppress obesity and associated inflammation via the AMPKα1/SIRT1 signaling pathway in rats fed a HFD.

Keywords: 5′-adenosine monophosphate-activated protein kinase catalytic subunit α-1; high-fat diet; inflammation; quercetin; resveratrol; sirtuin 1.

Figure 1.

Treatment with CQR reduces the body and visceral fat weights of rats fed a HFD. Rats were fed a ND, a HFD or a HFD+CQR for a period of 11 weeks. Subsequently (A) body weight, (B) food intake, (C) energy intake and (D) white adipose tissue weights were measured. (E) EAT morphology was observed using a light microscope at a magnification of ×200 and the (F) adipocyte diameters in EAT were measured. Data are expressed as the mean ± standard error of mean. *P<0.05, **P<0.01 and ***P<0.001 vs. ND. ^#P<0.05 and ^###P<0.001 vs. HFD. CQR, combination of quercetin and resveratrol; HFD, high fat diet; ND, normal diet; EAT, epididymal adipose tissues.

Figure 2.

Treatment with CQR reduces the clustering of mast cells in the epididymal adipose tissue (EAT). At 11 weeks, tissue samples were collected and (A) epididymal white adipose tissue was observed using a light microscope (small box: magnification, ×200, big box: magnification, ×100) following toluidine blue staining of the mast cells indicated by the blue stain. Pink plaques are erythrocytes and leukocytes in the blood vessels of EAT. Erythrocytes are cells without a nucleus, while leukocytes are cells with a nucleus. (B) Quantification of mast cells in the indicated groups was performed by observing the slides, n=8 per group. *P<0.05 and ^#P<0.05. All data are presented as the mean ± standard error of mean. CQR, combination of quercetin and resveratrol; HFD, high fat diet; ND, normal diet.

Figure 3.

Treatment with CQR increases AMPKα1 phosphorylation and SIRT1 expression in the EAT of rats fed a HFD. After 11 weeks, tissue samples were obtained from each group and the (A) protein and phosphorylation levels of AMPKα1 and (B) the protein expression of SIRT1 in EATs, were measured. Quantification of AMPKα1 activity and SIRT1 expression was presented as the ratio of pAMPKα1 to total AMPKα1 and SIRT1 to β-actin, respectively. Statistical differences between groups were identified using a one-way ANOVA test followed by Tukey's multiple comparison test (n=8 per group). All data are presented as the mean ± standard error of mean. ***P<0.001 and ^#P<0.05. AMPKα1, 5′-adenosine monophosphate-activated protein kinase α1; SIRT1, sirtuin 1; EAT, epididymal adipose tissue; HFD, high fat diet; ND, normal diet; CQR, combination of quercetin and resveratrol; p, phosphorylated.