- Basic Research
- Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice
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Songling Jiang, Md Jamal Uddin, Xiaoying Yu, Lingjuan Piao, Debra Dorotea, Goo Taeg Oh, Hunjoo Ha
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Diabetes Metab J. 2022;46(6):829-842. Published online June 24, 2022
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DOI: https://doi.org/10.4093/dmj.2021.0274
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 Abstract
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- Background
Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes. Peroxisomes are single membrane-enclosed organelles that play a role in the metabolism of lipid and reactive oxygen species. The present study examined the role of peroxisomes in high-fat diet (HFD)-induced NAFLD using fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist.
Methods
Eight-week-old male C57BL/6J mice were fed either a normal diet or HFD for 12 weeks, and fenofibrate (50 mg/kg/day) was orally administered along with the initiation of HFD.
Results
HFD-induced liver injury as measured by increased alanine aminotransferase, inflammation, oxidative stress, and lipid accumulation was effectively prevented by fenofibrate. Fenofibrate significantly increased the expression of peroxisomal genes and proteins involved in peroxisomal biogenesis and function. HFD-induced attenuation of peroxisomal fatty acid oxidation was also significantly restored by fenofibrate, demonstrating the functional significance of peroxisomal fatty acid oxidation. In Ppara deficient mice, fenofibrate failed to maintain peroxisomal biogenesis and function in HFD-induced liver injury.
Conclusion
The present data highlight the importance of PPARα-mediated peroxisomal fitness in the protective effect of fenofibrate against NAFLD.
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Citations
Citations to this article as recorded by  - PEX11B palmitoylation couples peroxisomal dysfunction with Schwann cells fail in diabetic neuropathy
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Diabetes & Metabolism Journal.2024; 48(2): 184. CrossRef - Lactobacillus plantarum NCHBL-004 modulates high-fat diet–induced weight gain and enhances GLP-1 production for blood glucose regulation
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Biology.2024; 13(12): 1027. CrossRef - Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD
Manuela Vitulo, Elisa Gnodi, Giulia Rosini, Raffaella Meneveri, Roberto Giovannoni, Donatella Barisani
International Journal of Molecular Sciences.2023; 24(16): 12748. CrossRef - PPARα agonist fenofibrate prevents postoperative cognitive dysfunction by enhancing fatty acid oxidation in mice
Tiantian Liu, Xinlu Chen, Ziqi Wei, Xue Han, Yujia Liu, Zhengliang Ma, Tianjiao Xia, Xiaoping Gu
Translational Neuroscience.2023;[Epub] CrossRef - Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet
Ying Zhang, Xiu-Bin Jia, Yun-Chao Liu, Wen-Qian Yu, Yan-Hong Si, Shou-Dong Guo
Frontiers in Nutrition.2022;[Epub] CrossRef
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