title: Activation of PPARγ by a Natural Flavonoid Modulator, Apigenin Ameliorates Obesity-Related Inflammation Via Regulation of Macrophage Polarization.
abstract: PPARγ has emerged as a master regulator of macrophage polarization and is the molecular target of the thiazolidinedione drugs. Here we show that apigenin binds and activates PPARγ by acting as a modulator. Activation of PPARγ by apigenin blocks p65 translocation into nuclei through inhibition of p65/PPARγ complex translocation into nuclei, thereby decreasing NF-κB activation and favoringM2 macrophage polarization. In HFD and ob/ob mice, apigenin significantly reverses M1 macrophage into M2 and reduces the infiltration of inflammatory cells in liver and adipose tissues, as well as decreases the levels of pro-inflammatory cytokines, thereby alleviating inflammation. Strikingly, apigenin reduces liver and muscular steatosis, decreases the levels of ALT, AST, TC and TG, improving glucose resistance obviously. Unlike rosiglitazone, apigenin does not cause significant weight gain, osteoporosis et al. Our findings identify apigenin as a modulator of PPARγ and a potential lead compound for treatment of metabolic disorders.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Xiujing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing 210094, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Weng
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Graduate Medical Education, Virginia Mason Medical Center, Seattle, WA 98101, USA.
authors.forename: Young D
authors.initials: YD
authors.lastname: Owen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Haohan
authors.initials: H
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Jingfa
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.lastname: WenYu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210046, China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Nanfei
authors.initials: N
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Dianhua
authors.initials: D
authors.lastname: Chen
authors.affiliation: Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210046, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China.
authors.forename: Renxiang
authors.initials: R
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of life Sciences, Nanjing University, Nanjing 210046, China; MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210046, China. Electronic address: ppshen@nju.edu.cn.
authors.forename: Pingping
authors.initials: P
authors.lastname: Shen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016130:Immunophenotyping; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D047310:Apigenin
keywords: Apigenin; Macrophage polarization; NF-κB; Obesity-related inflammation; PPARγ