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过氧化物酶体增殖物激活受体α:代谢综合征、神经退行性疾病和心血管疾病的新兴靶点。

PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases.

机构信息

Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Xiamen Key Laboratory of Cardiovascular Disease, Xiamen, China.

出版信息

Front Endocrinol (Lausanne). 2022 Dec 16;13:1074911. doi: 10.3389/fendo.2022.1074911. eCollection 2022.

Abstract

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is involved in lipid metabolism of various tissues. Different metabolites of fatty acids and agonists like fibrates activate PPARα for its transactivative or repressive function. PPARα is known to affect diverse human diseases, and we focus on advanced studies of its transcriptional regulation in these diseases. In MAFLD, PPARα shows a protective function with its upregulation of lipid oxidation and mitochondrial biogenesis and transcriptional repression of inflammatory genes, which is similar in Alzheimer's disease and cardiovascular disease. Activation of PPARα also prevents the progress of diabetes complications; however, its role in diabetes and cancers remains uncertain. Some PPARα-specific agonists, such as Wy14643 and fenofibrate, have been applied in metabolic syndrome treatment, which might own potential in wider application. Future studies may further explore the functions and interventions of PPARα in cancer, diabetes, immunological diseases, and neurodegenerative disease.

摘要

过氧化物酶体增殖物激活受体α(PPARα)是一种配体激活的转录因子,参与多种组织的脂质代谢。不同的脂肪酸代谢物和激动剂,如贝特类药物,激活 PPARα 发挥其转录激活或抑制功能。PPARα 已知与多种人类疾病有关,我们重点关注其在这些疾病中的转录调控的深入研究。在 MAFLD 中,PPARα 通过上调脂质氧化和线粒体生物发生以及转录抑制炎症基因发挥保护作用,这在阿尔茨海默病和心血管疾病中是相似的。激活 PPARα 还可以阻止糖尿病并发症的进展;然而,其在糖尿病和癌症中的作用仍不确定。一些 PPARα 特异性激动剂,如 Wy14643 和非诺贝特,已应用于代谢综合征的治疗,可能具有更广泛的应用潜力。未来的研究可能会进一步探索 PPARα 在癌症、糖尿病、免疫性疾病和神经退行性疾病中的功能和干预作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c99/9800994/475766d4bec4/fendo-13-1074911-g001.jpg

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