Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined. [provided by RefSeq, Jul 2008]
Forensic Context
A study in humans demonstrated that the PPARA gene encodes a circular RNA, hsa_circ_0116795 (circ_PPARA), which is highly expressed in the peripheral blood of patients with acute myocardial infarction (AMI) and in hypoxic human cardiomyocytes, is resistant to RNase R, and shows an area under the curve of 0.876 in ROC analysis for distinguishing AMI patients from healthy controls [Huang et al. DOI:10.1186/s40001-024-01753-3]. Another human study found that the PPARA transcription factor had low expression in the peripheral blood of sepsis patients, where its expression was positively correlated with 28-day survival rate, and it was identified as a core protein in a PPI network related to cytokine-mediated signaling pathways [Liu et al. DOI:10.0000000000002072]. A study in mice, rats, and other models demonstrated that the PPARA is transiently increased at wound edges after skin injury and its activation preserves kidney structure and reduces inflammation after ischemia/reperfusion injury, with protective effects also reported in liver, brain, and heart models [Michalik, L.; Wahli, W. DOI:10.1172/JCI27958]. In human sepsis patients, RNA-seq analysis of peripheral blood showed the PPARA had low expression compared to healthy controls, and its expression level was positively correlated with patient survival rates, with single-cell sequencing localizing its expression to monocyte, NK-T, and B cell lines [Liu, Jitao; Li, Shaolan; Xiong, Dianhui; Shang, Wenjun; Zhan, Tao; Zhu, Xingxin; He, Sheng; Wang, Yu; Zhang, Qian; Hu, Yingchun DOI:10.0000000000002072].