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Review
. 2023 Nov 13;15(22):4772.
doi: 10.3390/nu15224772.

Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders

Ping Hu  1 , Kaiqi Li  1 , Xiaoxu Peng  1 , Yufei Kan  1 , Hao Li  1 , Yanli Zhu  1 , Ziyu Wang  1 , Zhaojian Li  1 , Hao-Yu Liu  1   2 , Demin Cai  1   2
Affiliations
Review

Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders

Ping Hu et al. Nutrients. .

Abstract

Lipid metabolic diseases have substantial morbidity and mortality rates, posing a significant threat to human health. PPARα, a member of the peroxisome proliferator-activated receptors (PPARs), plays a crucial role in lipid metabolism and immune regulation. Recent studies have increasingly recognized the pivotal involvement of PPARα in diverse pathological conditions. This comprehensive review aims to elucidate the multifaceted role of PPARα in metabolic diseases including liver diseases, diabetes-related diseases, age-related diseases, and cancers, shedding light on the underlying molecular mechanisms and some regulatory effects of natural/synthetic ligands of PPARα. By summarizing the latest research findings on PPARα, we aim to provide a foundation for the possible therapeutic exploitation of PPARα in lipid metabolic diseases.

Keywords: PPARα; cancer; cell senescence; diabetes-related diseases; lipid metabolism; metabolic disorders.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration depicting the molecular mechanisms of PPARα modulate hepatic steatosis. (A): PPARα binds to specific PPREs as a heterodimer with RXR and then regulates fatty acids oxidation under physiological condition. (B): PPARα-mediated the actions of dietary interferences on lipid biosynthesis and fatty acid oxidation by epigenetic modulations. (C): The regulation mechanism of PPARα in directing abnormal lipogenesis, fatty acids oxidation, and cholesterogenesis via the recruitment of histone marks and co-factors when compose a novel and “atypical” transcription factors crosstalk at both the gene promoter and the enhancer.
Figure 2
Figure 2
PPARα might serve as a therapeutic target in the pathological processes of liver disease, age-related diseases, diabetes-related diseases, and several cancers by interacting with transcription factors, binding to specific ligands, and participating in cellular physiological processes.
See this image and copyright information in PMC

References

    1. Dewidar B., Kahl S., Pafili K., Roden M. Metabolic liver disease in diabetes—From mechanisms to clinical trials. Metabolism. 2020;111:154299. doi: 10.1016/j.metabol.2020.154299. - DOI - PMC - PubMed
    1. Amorim J.A., Coppotelli G., Rolo A.P., Palmeira C.M., Ross J.M., Sinclair D.A. Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat. Rev. Endocrinol. 2022;18:243–258. doi: 10.1038/s41574-021-00626-7. - DOI - PMC - PubMed
    1. Leone R.D., Powell J.D. Metabolism of immune cells in cancer. Nat. Rev. Cancer. 2020;20:516–531. doi: 10.1038/s41568-020-0273-y. - DOI - PMC - PubMed
    1. Faubert B., Solmonson A., DeBerardinis R.J. Metabolic reprogramming and cancer progression. Science. 2020;368:eaaw5473. doi: 10.1126/science.aaw5473. - DOI - PMC - PubMed
    1. Martinez-Reyes I., Chandel N.S. Cancer metabolism: Looking forward. Nat. Rev. Cancer. 2021;21:669–680. doi: 10.1038/s41568-021-00378-6. - DOI - PubMed