Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease

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Ran, Li-Sha
Wu, Ya-Zeng
Gan, Yi-Wen
Wang, Hong-Lian
Wu, Li-Juan
Zheng, Chun-Mei
Ming, Yao
Xiong, Ran
Li, Yong-Lin
Lei, Shi-Hang
Wang, Xue
Lao, Xiao-Qing
Zhang, Hong-Min
Wang, Li
Chen, Chen
et al.
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2022
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Abstract

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

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Journal of Natural Medicines

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© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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Gastroenterology and hepatology

Andrographolide

FATP2

Fatty acid uptake

Hepatic steatosis

NAFLD

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Ran, L-S; Wu, Y-Z; Gan, Y-W; Wang, H-L; Wu, L-J; Zheng, C-M; Ming, Y; Xiong, R; Li, Y-L; Lei, S-H; Wang, X; Lao, X-Q; Zhang, H-M; Wang, L; Chen, C; Zhao, C-Y, Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease, Journal of Natural Medicines, 2022

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