title: Pu'erh tea extract-mediated protection against hepatosteatosis and insulin resistance in mice with diet-induced obesity is associated with the induction of de novo lipogenesis in visceral adipose tissue.
abstract: BACKGROUND
  White adipose tissue (WAT) is important for the maintenance of metabolic homeostasis, and metabolic syndrome is sometimes associated with WAT dysfunction in humans and animals. WAT reportedly plays a key, beneficial role in the maintenance of glucose and lipid homeostasis during de novo lipogenesis (DNL). Pu'erh tea extract (PTE) can inhibit harmful, ectopic DNL in the liver, thus protecting against hepatosteatosis, in mice with diet-induced obesity. We examined whether PTE could induce DNL in WAT and consequently protect against hepatosteatosis.
  
  
  METHODS
  C57BL/6 male mice were fed a high-fat diet (HFD) with/without PTE for 16 weeks. Systemic insulin sensitivity was determined using HOMA-IR, insulin- and glucose-tolerance tests, and WAT adipogenesis was evaluated by histological analysis. Adipogenesis-, inflammation-, and DNL-related gene expression in visceral AT (VAT) and subcutaneous AT (SAT) was measured using quantitative reverse transcription-PCR. Regression analysis was used to investigate the association between DNL in WAT and systemic insulin resistance or hepatosteatosis.
  
  
  RESULTS
  Pu'erh tea extract significantly reduced the gain of body weight and SAT, but not VAT adiposity, in mice fed the high-fat diet and induced adipogenesis in VAT. The expression of DNL-related genes, including Glut4, encoding an important insulin-regulated glucose transporter (GLUT4), were highly elevated in VAT. Moreover, PTE inhibited VAT inflammation by simultaneously downregulating inflammatory molecules and inducing expression of Gpr120 that encodes an anti-inflammatory and pro-adipogenesis receptor (GPR-120) that recognizes unsaturated long-chain fatty acids, including DNL products. The expression of DNL-related genes in VAT was inversely correlated with hepatosteatosis and systemic insulin resistance.
  
  
  CONCLUSIONS
  Activation of DNL in VAT may explain PTE-mediated alleviation of hepatosteatosis symptoms and systemic insulin resistance.
authors.affiliation: Department of Internal Medicine, 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 Microbiology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.|Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.|Key Laboratory of Pu-erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming, 650201, China.
authors.forename: Chongye
authors.initials: C
authors.lastname: Fang
authors.affiliation: Yunnan University, Kunming, China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Hao
authors.affiliation: Key Laboratory of Pu-erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming, 650201, China.|State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming, China.
authors.forename: Xuanjun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, 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: Department of Microbiology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.|Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Key Laboratory of Pu-erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming, 650201, China. shengjunpuer@yahoo.com.cn.|State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming, China. shengjunpuer@yahoo.com.cn.|Pu'erh Tea Research Institute, Pu'erh, China. shengjunpuer@yahoo.com.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Sheng
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000517:prevention & control*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013662:Tea / Q000737:chemistry*
chemical_list: D007328:Insulin; D010936:Plant Extracts; D013662:Tea; D005947:Glucose
keywords: De novo lipogenesis; Hepatosteatosis; Insulin resistance; Pu’erh tea extract; Visceral adipose tissue