Xianbin Cai1,2,3, Chongye Fang2,4, Shuhei Hayashi2,3, Shumei Hao5, Mingming Zhao6, Hiroko Tsutsui2,3, Shuhei Nishiguchi7, Jun Sheng8. 1. Division of Hepatobiliary and Pancreatic Diseases, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 2. Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 3. Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. 4. Key Laboratory of Pu-erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming, 650201, People's Republic of China. 5. Yunnan University, Kunming, 650091, People's Republic of China. 6. Center for iPS Cell Research and Application (CiRA), Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan. 7. Division of Hepatobiliary and Pancreatic Diseases, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. nishiguc@hyo-med.ac.jp. 8. 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.
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.
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: Mariana Lazo; Ruben Hernaez; Mark S Eberhardt; Susanne Bonekamp; Ihab Kamel; Eliseo Guallar; Ayman Koteish; Frederick L Brancati; Jeanne M Clark Journal: Am J Epidemiol Date: 2013-05-23 Impact factor: 4.897