Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1.
Adipose tissue macrophage (ATM) plays a central role in obesity-associated inflammation and insulin resistance. Quercetin, a dietary flavonoid, possesses anti-inflammation and anti-insulin resistance properties. However, it is unclear whether quercetin can alleviate high-fat diet (HFD)-induced ATM infiltration and inflammation in mice. In this study, 5-week-old C57BL/6 mice were fed low-fat diet, HFD, or HFD with 0.l% quercetin for 12 weeks, respectively. Dietary quercetin reduced HFD-induced body weight gain and improved insulin sensitivity and glucose intolerance in mice. Meanwhile, dietary quercetin enhanced glucose transporter 4 translocation and protein kinase B signal in epididymis adipose tissues (EATs), suggesting that it heightened glucose uptake in adipose tissues. Histological and real-time PCR analysis revealed that quercetin attenuated mast cell and macrophage infiltration into EATs in HFD-fed mice. Dietary quercetin also modified the phenotype ratio of M1/M2 macrophages, lowered the levels of proinflammatory cytokines, and enhanced adenosine monophosphate-activated protein kinase (AMPK) α1 phosphorylation and silent information regulator 1 (SIRT1) expression in EATs. Further, using AMPK activator 5-aminoimidazole-4-carboxamide-1-β4-ribofuranoside and inhibitor Compound C, we found that quercetin inhibited polarization and inflammation of mouse bone marrow-derived macrophages through an AMPKα1/SIRT1-mediated mechanism. In conclusion, dietary quercetin might suppress ATM infiltration and inflammation through the AMPKα1/SIRT1 pathway in HFD-fed mice.
School of Biotechnology & Food Engineering, Hefei University of Technology, Hefei 230009, China.
Jing
J
Dong
Xian
X
Zhang
Lei
L
Zhang
Hui-Xi
HX
Bian
Na
N
Xu
Bin
B
Bao
Jian
J
Liu
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007249:Inflammation / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011794:Quercetin / Q000008:administration & dosage / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
D016207:Cytokines; D051275:Glucose Transporter Type 4; D011794:Quercetin; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
adenosine monophosphate-activated protein kinase α1/silent information regulator 1; adipose tissue macrophage; insulin resistance; macrophages; obesity