Study On The Role And Mechanism Of Quercetin In Adipose Tissue Macrophage Infiltration And Inflammation In Mice

The metabolic abnormalities of obesity will lead to insulin resistance,dyslipidemia and hypertension characterized as the metabolic syndrome, all welldocumented as a risk factor for cardiovascular disease. Both diet-induced obesityand diabetes are linked to the chronic low grade inflammation in white adiposetissues and adipose tissue macrophages (ATMs) have an essential role inobesity-associated inflammation and insulin resistance. Researches havedemonstrated that chronic inflammation becomes a therapeutic target of insulinresistance, T2D, and cardiovascular disease in humans and rodents. Quercetin, animportant dietary flavonoid, has showed anti-inflammatory and anti-insulinresistance properties in experiment animals and in vitro conditions. However, it isunclear whether quercetin could alleviate high fat diet (HFD) induced ATMinfiltration and inflammation in mice. Studying the effects and related mechanisms,not only enrich the theory about plant flavonoid nutrition, but also supply apreliminary guiding principle for the development of quercetin-containedfunctional food.To confirm the effects of dietary quercetin on obesity and diabetes,five-week-old C57BL/6mice were fed low fat diet (LFD), high fat diet (HFD) with0.02or0.l%quercetin for12weeks, respectively. Dietary quercetin reducedHFD-induced body weight gain and fat deposition. Meanwhile, the mice fedquercetin-contained HFD had improved insulin sensitivity and glucose tolerancecompared with mice fed only HFD, along with their enhancement of GLUT4expression and Akt signal in epididymis adipose tissues (EAT). The down-regulatedeffect of quercetin on level of insulin and leptin in serum and the up-regulatedeffect on adiponectin both in serum and adipose tissue further suggested theimprovement effect of quercetin on insulin resistance. Histological and real-timePCR analysis revealed that quercetin attenuated mast cell and macrophageinfiltrations into EAT, decreased expression of M1macrophage mark genes Nos2and Cd11c in EAT, increased expression of M2macrophage mark genes Mgl2andChi3l3, and lowered the levels of pro-inflammatory cytokines MCP-1, TNF-α and IL-6in EAT and serum. Moreover, dietary quercetin promoted the adipose tissueAMPKα1and SIRT1expression in the mice with HFD. Further, uilitizing mousebone marrow-derived macrophages (BMDMs), we confirmed in vitro the inhibitionaction of quercetin on macrophage inflammation and polarization. The mechanisticstudy showed quercetin increased macrophage AMPKα1phosphorylation andSIRT1mRNA expression in BMDMs with or without LPS activation. Theses resultssuggest that quercetin regulated macrophage polarization and inflammation throughactivating AMPKα1/SIRT1.In conclusion, dietary quercetin suppressed ATM infiltration and inflammation,and might hereby ameliorate obesity-associated insulin resistance in mice.Quercetin as a naturally occurring flavonoids compound may be a useful dietarysupplement to ameliorate diet-induced obesity and insulin resistance.