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Trivalent chromium alleviates oleic acid induced steatosis in SMMC-7721 cells by decreasing fatty acid uptake and triglyceride synthesis

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Abstract

Trivalent chromium [Cr(III)] has been shown as an essential trace element for human health. Previous studies depict that Cr(III) plays important roles in maintaining normal glucose and lipid metabolism, whereas its effect on the hepatic lipid metabolism is still unknown. In the present study, we investigated the effects and underlying mechanisms of Cr on hepatic steatosis induced by oleic acid (OA) in human hepatoma SMMC-7721 cells. Hepatic steatosis model was co-administered with Cr. Indexes of lipid accumulation were determined and associated genes expression were analyzed. The data showed that OA could induce lipid accumulation and triglyceride (TG) content in SMMC-7721 cells, and significantly increase the expression of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2). This steatosis effect of OA was ameliorated by Cr. The TG accumulation and up-regulation of CD36 and DGAT2 genes followed steatosis induction were inhibited by Cr. After the treatment of Cr, excessive intracellular OA content was also attenuated. Furthermore, Cr still performed inhibitory effect of DGAT2 expression at the presence of DGAT2 agonist or inhibitor, which indicated that the inhibitory effect of Cr on lipogenesis is associated with the downregulation of DGAT2 expression. These findings demonstrate that Cr alleviates hepatic steatosis via suppressing CD36 expression to prevent fatty acid uptake, as well as suppressing DGAT2 expression to inhibit TG synthesis. It suggests that CD36 and DGAT2 might become the novel drug targets for their properties in hepatic steatosis. Most importantly, Cr may be a potential anti-steatosis candidate to offer protective effects against liver damage.

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Acknowledgments

This work was sponsored by grants from Shanghai Scientific and Technological Innovation Project (14520720700), the Natural Science Foundation of Shanghai (15ZR1400200), State Education Ministry and Fundamental Research Funds for the Central Universities (222201313010 and 2232014A3-03), the Applied Basic Research Project of Promotion Plan for Scientific and Technological Innovation in Qinghai Province (2015-ZJ-703).

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  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, People’s Republic of China

    Song Wang, Jian Wang, Xiaonan Zhang, Linlin Hu & Ping Shi

  2. College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, People’s Republic of China

    Zhijia Fang & Zhiwei Huang

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  1. Song Wang
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  2. Jian Wang
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  3. Xiaonan Zhang
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Correspondence to Ping Shi.

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Wang, S., Wang, J., Zhang, X. et al. Trivalent chromium alleviates oleic acid induced steatosis in SMMC-7721 cells by decreasing fatty acid uptake and triglyceride synthesis. Biometals 29, 881–892 (2016). https://doi.org/10.1007/s10534-016-9960-2

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