title: Pu-erh tea extract ameliorates high-fat diet-induced nonalcoholic steatohepatitis and insulin resistance by modulating hepatic IL-6/STAT3 signaling in mice.
abstract: BACKGROUND
  Pu-erh tea, made from the leaves of Camellia sinensis, possesses activities beneficial for human health, including anti-inflammatory, anti-oxidant, and anti-obesity properties.
  
  
  OBJECTIVE
  We investigated the effects of a pu-erh tea extract (PTE) on nonalcoholic steatohepatitis (NASH) and the molecular mechanisms underlying such effects.
  
  
  METHODS
  Eight-week-old male C57BL/6J mice were fed a normal chow diet or high-fat diet (HFD) for 17 weeks, during which PTE was simultaneously administered in drinking water. Body weight, hepatic inflammation, steatosis, insulin sensitivity, expression of lipogenesis- and gluconeogenesis-associated genes, and signal transducer and activator of transcription (STAT)-3 phosphorylation were examined. The anti-steatotic effects of PTE and/or interleukin (IL)-6 were evaluated in HepG2 cells. The lipid accumulation, STAT3 phosphorylation, and expression of lipid metabolism-related genes were analyzed.
  
  
  RESULTS
  PTE inhibited HFD-induced obesity and significantly attenuated HFD-induced hepatic steatosis and liver inflammation, and prevented against liver injury. PTE treatment improved glucose tolerance and insulin sensitivity in HFD-fed mice. Moreover, PTE treatment maintained the intact insulin signal and significantly decreased expression of gluconeogenesis-related genes in the livers of HFD-fed mice. PTE treatment strikingly enhanced STAT3 phosphorylation in the livers of HFD-fed mice. Consistent with this increase in STAT3 phosphorylation, pre-treatment of HepG2 cells with PTE enhanced IL-6-induced STAT3 phosphorylation and attenuated oleic acid-induced steatosis in a STAT3-dependent manner. In contrast, PTE inhibited IL-6-induced STAT3 phosphorylation in macrophages.
  
  
  CONCLUSIONS
  PTE ameliorates hepatic lipid metabolism, inflammation, and insulin resistance in mice with HFD-induced NASH, presumably by modulating hepatic IL-6/STAT3 signaling.
authors.affiliation: Division of Hepatobiliary and Pancreatic Diseases, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Xianbin
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Key Laboratory of Pu-erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming, 650201, People's Republic of China.
authors.forename: Chongye
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Yunnan University, Kunming, 650091, People's Republic of China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Hao
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.|Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Division of Hepatobiliary and Pancreatic Diseases, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. nishiguc@hyo-med.ac.jp.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
authors.affiliation: Key Laboratory of Pu-erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming, 650201, People's Republic of China. shengjunpuer@yahoo.com.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Sheng
mesh_terms: D000818:Animals; D028241:Camellia sinensis; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects; D005243:Feces / Q000737:chemistry; D005951:Glucose Tolerance Test; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013662:Tea; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015850:Interleukin-6; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D013662:Tea; C577686:interleukin-6, mouse
keywords: Insulin resistance; NASH; PTE; STAT3