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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

  • Original Article—Liver, Pancreas, and Biliary Tract
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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.

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Acknowledgements

We thank Nana Iwami, Keiko Mitani, and Tomoko Mizobuchi for their excellent technical assistance. We also thank Qin Yang and Koubun Yasuda for helpful discussions. Xianbin Cai was supported by the State Scholarship Fund of China Scholarship Council (CSC). This study was partly supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2012–2015 and by the Pu’erh Tea Research Institute (Yunnan, China).

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    Authors and Affiliations

    1. Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

      Xianbin Cai & Shuhei Nishiguchi

    2. Department of Microbiology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

      Shuhei Hayashi & Hiroko Tsutsui

    3. Department of Pu-erh Tea and Medical Science, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

      Shuhei Hayashi, Chongye Fang & Hiroko Tsutsui

    4. Key Laboratory of Pu-erh Tea Science, The Ministry of Education, Yunnan Agricultural University, Kunming, 650201, China

      Chongye Fang, Xuanjun Wang & Jun Sheng

    5. Yunnan University, Kunming, China

      Shumei Hao

    6. State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Kunming, China

      Xuanjun Wang & Jun Sheng

    7. Pu’erh Tea Research Institute, Pu’erh, China

      Jun Sheng

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    1. Xianbin Cai
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    X. Cai and S. Hayashi contributed equally to this work.

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    Cai, X., Hayashi, S., Fang, C. et al. 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. J Gastroenterol 52, 1240–1251 (2017). https://doi.org/10.1007/s00535-017-1332-3

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