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Bavachin protects against diet-induced hepatic steatosis and obesity in mice

Acta Pharmacologica Sinica volume 44, pages 1416–1428 (2023)Cite this article

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major health concern worldwide, and the incidence of metabolic disorders associated with NAFLD is rapidly increasing because of the obesity epidemic. There are currently no approved drugs that prevent or treat NAFLD. Recent evidence shows that bavachin, a flavonoid isolated from the seeds and fruits of Psoralea corylifolia L., increases the transcriptional activity of PPARγ and insulin sensitivity during preadipocyte differentiation, but the effect of bavachin on glucose and lipid metabolism remains unclear. In the current study we investigated the effects of bavachin on obesity-associated NAFLD in vivo and in vitro. In mouse primary hepatocytes and Huh7 cells, treatment with bavachin (20 μM) significantly suppressed PA/OA or high glucose/high insulin-induced increases in the expression of fatty acid synthesis-related genes and the number and size of lipid droplets. Furthermore, bavachin treatment markedly elevated the phosphorylation levels of AKT and GSK-3β, improving the insulin signaling activity in the cells. In HFD-induced obese mice, administration of bavachin (30 mg/kg, i.p. every other day for 8 weeks) efficiently attenuated the increases in body weight, liver weight, blood glucose, and liver and serum triglyceride contents. Moreover, bavachin administration significantly alleviated hepatic inflammation and ameliorated HFD-induced glucose intolerance and insulin resistance. We demonstrated that bavachin protected against HFD-induced obesity by inducing fat thermogenesis and browning subcutaneous white adipose tissue (subWAT). We revealed that bavachin repressed the expression of lipid synthesis genes in the liver of obese mice, while promoting the expression of thermogenesis, browning, and mitochondrial respiration-related genes in subWAT and brown adipose tissue (BAT) in the mice. In conclusion, bavachin attenuates hepatic steatosis and obesity by repressing de novo lipogenesis, inducing fat thermogenesis and browning subWAT, suggesting that bavachin is a potential drug for NAFLD therapy.

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Fig. 1: Bavachin attenuates lipid accumulation in primary mouse hepatocytes and Huh7 cells.
Fig. 2: Bavachin improves insulin sensitivity in vitro.
Fig. 3: Bavachin ameliorates hepatic steatosis caused by HFD feeding.
Fig. 4: Bavachin represses the hepatic lipogenesis in HFD-induced mice.
Fig. 5: Bavachin improves glucose homeostasis and insulin resistance in HFD-fed mice.
Fig. 6: Bavachin alleviates HFD-induced hepatic inflammation.
Fig. 7: Bavachin increases thermogenesis and browning of the white adipose tissue in mice fed HFD.

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Acknowledgements

This work was supported by collective grants from the National Natural Science Foundation of China (No. 81870402 and 81670517), Anhui Science Fund for Distinguished Young Scholars (No. 2208085J45), Key Research and Development Program of Anhui Province (No. 2022i01020023), Research Fund of Anhui Institute of translational medicine (No. 2022zhyx-C12) and the Project Funded by Scientific Research Platform and Base Upgrading Plan of Anhui Medical University (No. 2021xkjT048).

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  1. These authors contributed equally: Xiang Wei, Li Lin, Qian-qian Yuan

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University, Hefei, 230032, China

    Xiang Wei, Li Lin, Qian-qian Yuan, Xiu-yun Wang, Qing Zhang, Xiao-min Zhang, Ke-chao Tang, Man-yu Guo & Hua-bing Zhang

  2. Department of Hyperbaric Oxygen, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, China

    Xiang Wei & Yin-liang Qi

  3. The Second Clinical Medical College of Anhui Medical University, Hefei, 230032, China

    Ting-yu Dong

  4. Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

    Wei Han

  5. Synthetic Laboratory of School of Basic Medicine Sciences, Anhui Medical University, Hefei, 230032, China

    Da-ke Huang

  6. Health Management Center, The First Affiliated Hospital of the University of Sciences and Technology of China (Anhui Provincial Hospital), Hefei, 230001, China

    Mei Zhang

  7. The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou), Chuzhou, 239001, China

    Hua-bing Zhang

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Contributions

HBZ and MZ designed the research and revised the paper. XW, LL, QQY, XYW, QZ, XMZ, KCT, MYG, TYD, WH, DKH and YLQ performed experiments. XW and HBZ analysed the data. XW wrote the paper. HBZ and MZ reviewed the paper.

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Wei, X., Lin, L., Yuan, Qq. et al. Bavachin protects against diet-induced hepatic steatosis and obesity in mice. Acta Pharmacol Sin 44, 1416–1428 (2023). https://doi.org/10.1038/s41401-023-01056-z

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