PPAR Research
 Journal metrics
Acceptance rate44%
Submission to final decision48 days
Acceptance to publication38 days
CiteScore6.300
Journal Citation Indicator0.890
Impact Factor4.964

Oleoylethanolamide Alleviates Hepatic Ischemia-Reperfusion Injury via Inhibiting Endoplasmic Reticulum Stress-Associated Apoptosis

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PPAR Research publishes articles related to mechanisms involved in the activation of peroxisome proliferator-activated receptors, as well as their role in regulation of cellular differentiation, development, energy homeostasis and metabolic function.

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Research Article

Explore the Role of the rs1801133-PPARG Pathway in the H-type Hypertension

Both rs1801133 mutation on Methylenetetrahydrofolate reductase (MTHFR) gene and transcription factor peroxisome proliferator-activated gamma (PPARG) have been associated with plasma homocysteine (Hcy) levels and hypertension. However, their role in H-type hypertension remains unclear. In this study, we first tested the association between rs1801133 genotypes and Hcy level in H-type hypertension using clinical profiles collected from 203 patients before and after the treatment using enalapril maleate and folic acid tablets (EMFAT). Then, we constructed a literature-based pathway analysis to explore the role of the rs1801133-PPARG signaling pathway in H-type hypertension and its treatment. Although presented similar blood pressure, the patients with TT genotype of rs1801133 were much younger ( value <0.05) and significantly higher in Hcy levels ( and ) than that in the CC and CT genotype groups. Pathway analysis showed that T-allele of rs1801133 could inhibit the expression of PPARG through the downregulation of folate levels and upregulation of Hcy levels, which increased the risk of hypertension and hyperhomocysteinemia. Treatment using EMFAT led to similarly decreased Hcy levels for all patients with different genotypes (; ), which may occur partially through the activation of PPARG. Moreover, even after treatment, the patients with TT genotype still presented significantly higher Hcy levels ( and ). Our results supported that rs1801133 mutation could play a role in H-type hypertension, which might be partially through the downregulation of PPARG. Moreover, PPARG might also be involved in treating H-type hypertension using EMFAT.

Research Article

Increased PPARD Expression May Play a Protective Role in Human Lung Adenocarcinoma and Squamous Cell Carcinoma

Peroxisome proliferator-activated receptor-δ, encoded by gene PPARD, is overexpressed in a majority of human lung cancer subtypes, but its role in the tumor progression remains poorly understood. We have analyzed the expression of PPARD in lung adenocarcinoma (LA) and squamous cell carcinoma (LSCC) datasets. The potential roles of PPARD in the pathological development of LA and LSCC were explored through literature-based pathway analysis and pathway enrichment analysis. In all LA datasets () and in seven out of nine LSCC studies, the levels of PPARD were increased as compared to control tissues (log-fold changes were and for LA and LSCC, respectively). On average, the expression levels of PPARD in LA were higher than those in LSCC (). Pathway analysis showed that the overexpression of PPARD might play both positive and negative roles in the development of both LA and LSCC. Specifically, PPARD inhibits seven LSCC promoters and seven LA promoters and activates one LSCC inhibitor and another LA inhibitor. However, PPARD also activates six and one promoters of LA and LSCC, respectively, which would facilitate the development of LA/LSCC. Our results suggested a mixed role of PPARD in LA/LSCC, which may add new insights into the understanding of the PPARD-lung cancer relationship.

Research Article

Role of Apolipoprotein A1 in PPAR Signaling Pathway for Nonalcoholic Fatty Liver Disease

Peroxisome proliferator-activated receptors (PPARs) have been suggested to play crucial roles in the pathology of NAFLD with a vague understanding of the underlying mechanism. Here, we integrated large-scale literature data and clinical data to explore the potential role of the PPAR-APOA1 signaling pathway in the pathology of NAFLD. First, the signaling pathway connecting PPARs, APOA1, and NAFLD was constructed. Then, we employed clinical data to explore the association between APOA1 levels and NAFLD. In addition, we built the APOA1-driven pathway analysis to explore the potential mechanism of the APOA1-NAFLD association. Pathway analysis showed that APOA1 serves as a hubprotein connecting PPARs and NAFLD through a beneficial modulation of 16 out of 21 NAFLD upstream regulators. Each relationship within the composed pathway was supported by results from multiple previous studies. Clinical data analysis showed that an increase of APOA1 level was associated with a significantly decreased NAFLD prevalence (; ). When other confounding factors were adjusted, serum APOA1 level was shown as an independent risk factor for the prevalence of NAFLD ( value<.0001; ). Our results suggested that the three PPARs (PPARA, PPARD, and PPARG) might promote the expression and molecular transportation of APOA1 to form a PPAR-APOA1 signaling pathway that demonstrated a beneficial role in the pathogenesis of NAFLD.

Research Article

Comprehensive Analysis of Copy Number Variation, Nucleotide Mutation, and Transcription Level of PPAR Pathway-Related Genes in Endometrial Cancer

Endometrial cancer is a common malignant tumor in gynecology, and the prognosis of advanced patients is dismal. Recently, many studies on the peroxisome proliferator-activated receptor pathway have elucidated its crucial involvement in endometrial cancer. Copy number variation (CNA) and nucleotide mutations often occur in tumor tissues, leading to abnormal protein expression and changes in protein structure. We analyzed the exon sequencing data of endometrial cancer patients in the TCGA database and found that somatic changes in PPAR pathway-related genes (PPAR-related-gene) often occur in UCEC patients. Patients with CNA or mutation changes in the exon region of the PPAR-related-gene usually have different prognostic outcomes. Furthermore, we found that the mRNA transcription and protein translation levels of PPAR-related-gene in UCEC are significantly different from that of adjacent tissues/normal uterus. The transcription level of some PPAR-related-gene (DBI, CPT1A, CYP27A1, and ME1) is significantly linked to the prognosis of UCEC patients. We further constructed a prognostic predicting tool called PPAR Risk score, a prognostic prediction tool that is a strong independent risk factor for the overall survival rate of UCEC patients. Comparing to the typical TNM classification system, this tool has higher prediction accuracy. We created a nomogram by combining PPAR Risk score with clinical characteristics of patients in order to increase prediction accuracy and promote clinical use. In summary, our study demonstrated that PPAR-related-gene in UCEC had significant alterations in CNA, nucleotide mutations, and mRNA transcription levels. These findings can provide a fresh perspective for postoperative survival prediction and individualized therapy of UCEC patients.

Research Article

In Vivo and Ex Vivo Evaluation of 1,3-Thiazolidine-2,4-Dione Derivatives as Euglycemic Agents

Thiazolidinediones (TZDs), used to treat type 2 diabetes mellitus, act as full agonists of the peroxisome proliferator-activated receptor gamma. Unfortunately, they produce adverse effects, including weight gain, hepatic toxicity, and heart failure. Our group previously reported the design, synthesis, in silico evaluation, and acute oral toxicity test of two TZD derivatives, compounds 40 (C40) and 81 (C81), characterized as category 5 and 4, respectively, under the Globally Harmonized System. The aim of this study was to determine whether C40, C81, and a new compound, C4, act as euglycemic and antioxidant agents in male Wistar rats with streptozotocin-induced diabetes. The animals were randomly divided into six groups (): the control, those with diabetes and untreated, and those with diabetes and treated with pioglitazone, C40, C81, or C4 (daily for 21 days). At the end of the experiment, tissue samples were collected to quantify the level of glucose, insulin, triglycerides, total cholesterol, and liver enzymes, as well as enzymatic and nonenzymatic antioxidant activity. C4, without a hypoglycemic effect, displayed the best antioxidant activity. Whereas C81 could only attenuate the elevated level of blood glucose, C40 generated euglycemia by the end of the treatment. All compounds produced a significant decrease in triglycerides.

Research Article

Identification of a Novel PPAR Signature for Predicting Prognosis, Immune Microenvironment, and Chemotherapy Response in Bladder Cancer

Background. Mounting evidence has confirmed that peroxisome proliferator-activated receptors (PPARs) played a crucial role in the development and progression of bladder cancer (BLCA). The purpose of this study is to comprehensively investigate the function and prognostic value of PPAR-targeted genes in BLCA. Methods. The RNA sequencing data and clinical information of BLCA patients were acquired from The Cancer Genome Atlas (TCGA). The differentially expressed PPAR-targeted genes were investigated. Cox analysis and least absolute shrinkage and selection operator (LASSO) analysis were performed for screening prognostic PPAR-targeted genes and constructing the prognostic PPAR signature and then validated by GSE13507 cohort and GSE32894 cohort. A nomogram was constructed to predict the outcomes of BLCA patients in combination with PPAR signature and clinical factors. Gene set enrichment analysis (GSEA) and immune cell infiltration were implemented to explore the molecular characteristics of the signature. The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to predict the chemotherapy responses of the prognostic signature. The candidate small molecule drugs targeting PPAR-targeted genes were screened by the CMAP database. Results. We constructed and validated the prognostic signature comprising of 4 PPAR-targeted genes (CPT1B, CALR, AHNAK, and FADS2), which was an independent prognostic biomarker in BLCA patients. A nomogram based on the signature and clinical factors was established in the TCGA set, and the calibration plots displayed the excellent predictive capacity. GSEA analysis indicated that PPAR signature was implicated in multiple oncogenic signaling pathways and correlated with tumor immune cell infiltration. Patients in the high-risk groups showed greater sensitivity to chemotherapy than those in the low-risk groups. Moreover, 11 candidate small molecule drugs were identified for the treatment of BLCA. Conclusion. We constructed and validated a novel PPAR signature, which showed the excellent performance in predicting prognosis and chemotherapy sensitivity of BLCA patients.

PPAR Research
 Journal metrics
Acceptance rate44%
Submission to final decision48 days
Acceptance to publication38 days
CiteScore6.300
Journal Citation Indicator0.890
Impact Factor4.964
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