title: Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages.
abstract: Inflammatory polarisation of adipose tissue macrophages (ATMs) plays a critical role in the development of obesity-associated metabolic diseases such as insulin resistance and diabetes. Our previous study indicated that dietary luteolin (LU) could prevent the establishment of insulin resistance in mice fed a high-fat diet (HFD). Here, we further investigated the effects of LU, which is a natural flavonoid, on pre-established insulin resistance and obesity-associated ATM polarisation in mice.
  
  
  
  Five-week-old C57/BL6 mice were fed on a low-fat diet or HFD for 20 weeks, with some mice receiving supplementation with 0.01% LU from weeks 1 or 10 of the HFD to assess the actions of LU on insulin resistance and ATM polarisation. Furthermore, the role of LU in metabolic-dysfunction-associated macrophage phenotypes was investigated in vitro.
  
  
  
  Dietary LU supplementation, either for 20 weeks or from weeks 10 to 20 of an HFD, significantly improved insulin resistance in HFD-fed mice. In addition, inflammatory macrophage infiltration and polarisation were suppressed in mouse epididymal adipose tissues. Furthermore, LU treatment directly reversed lipopolysaccharide-stimulated and metabolism-regulated molecules, and induced inflammatory polarisation in mouse RAW264.7 cells and peritoneal cavity resident macrophages. Finally, using the selective AMP-activated protein kinase (AMPK) inhibitor compound C and Ampkα1 (also known as Prkaa1) silencing with siRNA, we found that LU activated AMPKα1 in macrophages to inhibit their inflammatory polarisation and enhanced insulin signals in adipocytes that were stimulated with macrophage-conditioned media.
  
  
  
  Dietary LU ameliorated insulin resistance in diet-induced obese mice by promoting AMPKα1 signalling in ATMs.
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui, 230009, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui, 230009, People's Republic of China.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Han
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui, 230009, People's Republic of China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui, 230009, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui, 230009, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Bao
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui, 230009, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei, Anhui, 230009, People's Republic of China. liujian509@hfut.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007333:Insulin Resistance / Q000502:physiology; D047311:Luteolin / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D047311:Luteolin
keywords: AMPKα1; Adipose tissue macrophage; Insulin resistance; Luteolin; Polarisation