title: Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance.
abstract: OBJECTIVE
  Insulin resistance is associated with a chronic inflammation in adipose tissue which is propagated by a phenotypic switch in adipose tissue macrophage (ATM) polarization. This study aimed to investigate whether berberine, the major alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting ATM activation and inflammatory response in adipose tissue.
  
  
  METHODS
  High-fat-diet induced obese mice were administered oral with berberine (50mg/kg/day) for 14days. ATMs were analysed using FACS and insulin resistance was evaluated. Expressions of pro-inflammatory cytokines and activation of inflammatory pathways were detected. The chemotaxis of macrophages was measured. Glucose consumption and insulin signalling of adipocytes were examined.
  
  
  RESULTS
  Berberine significantly decreased F4/80+/CD11c+/CD206-cells in the stromal vascular fraction from adipose tissue and improved glucose tolerance in obsess mice. In addition, berberine reduced the elevated levels of serum TNF-α, IL-6 and MCP-1 and the expressions of TNF-α, IL-6 and MCP-1 and attenuated the phosphorylation of JNK and IKKβ and the expression of NF-κB p65 in the obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively. The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased in berberine-treated adipose tissue. Conditioned medium from adipocytes treated with berberine reduced the number of infiltrated macrophages. Berberine partly restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in adipocytes induced by the activation of macrophages.
  
  
  CONCLUSIONS
  Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue.
authors.affiliation: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Department of Endocrinology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Ye
authors.affiliation: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Liang
authors.affiliation: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Xizhong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China; Department of Endocrinology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: wbshang@njucm.edu.cn.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Shang
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001599:Berberine / Q000627:therapeutic use*; D002460:Cell Line; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007333:Insulin Resistance; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D001599:Berberine
keywords: Adipose tissue; Berberine; Inflammation; Insulin resistance; Macrophage