Gemfibrozil reduces lipid accumulation in SMMC‑7721 cells via the involvement of PPARα and SREBP1

Zhang,Xiaonan; Wang,Song; Hu,Linlin; Wang,Jian; Liu,Yajing; Shi,Ping

doi:10.3892/etm.2018.7046

Gemfibrozil reduces lipid accumulation in SMMC‑7721 cells via the involvement of PPARα and SREBP1

Authors:
- Xiaonan Zhang
- Song Wang
- Linlin Hu
- Jian Wang
- Yajing Liu
- Ping Shi
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Affiliations: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P.R. China
Published online on: December 5, 2018 https://doi.org/10.3892/etm.2018.7046
Pages: 1282-1289
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gemfibrozil (GEM) is a member of the fibrate class of lipid‑lowering pharmaceuticals and has been widely used in the therapy of different forms of hyperlipidemia and hypercholesterolemia. Non‑alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is becoming an important public health concern worldwide. However, there is little knowledge about the effects of GEM on NAFLD. In the present study, oleate‑treated human hepatoma SMMC‑7721 cells were utilized to investigate the role of GEM in regulating hepatic lipid metabolism. The present results demonstrated that GEM attenuated excessive intracellular triglyceride content in the steatosis model. Upregulation of peroxisome proliferator‑activated receptor α (PPARα) protein and sterol regulatory element‑binding protein 1 (SREBP1) was detected following treatment with GEM. Additionally, reverse transcription‑polymerase chain reaction analysis demonstrated that GEM increased the downstream genes related to PPARα and SREBP1, including carnitine palmitoyltransferase 2, acyl‑coA oxidase 1, hydroxyacyl‑CoA dehydrogenase, LIPIN1 and diacylglycerol O‑acyltransferase 1. These findings demonstrated that GEM alleviated hepatic steatosis via the involvement of the PPARα and SREBP1 signaling pathways, which enhances lipid oxidation and interferes with lipid synthesis and secretion. Taken together, the data provide direct evidence that GEM may lower lipid accumulation in hepatocellular steatosis cells in vitro and that it may have a potential therapeutic use for NAFLD.

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