PPAR Research最新文献

{"title":"Clinical Relevance and Drug Modulation of PPAR Signaling Pathway in Triple-Negative Breast Cancer: A Comprehensive Analysis.","authors":"Yanxia Zhang, Yunduo Liu, Mei Zhang, Guanjie Li, Siling Zhu, Keping Xie, Bin Xiao, Linhai Li","doi":"10.1155/ppar/4164906","DOIUrl":"10.1155/ppar/4164906","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is highly heterogeneous and poses a significant medical challenge due to limited treatment options and poor outcomes. Peroxisome proliferator-activated receptors (PPARs) play a crucial role in regulating metabolism and cell fate. While the association between PPAR signal and human cancers has been a topic of concern, its specific relationship with TNBC remains unclear. Integrated analysis of large published datasets from clinical cohorts and cell lines through databases has proven to be a powerful and essential approach for understanding cancer and uncovering new molecular targets. Here, we conducted a comprehensive study investigating the clinical relevance and drug modulation of the PPAR signaling pathway in TNBC, using data from The Cancer Genome Atlas (TCGA) for TNBC patients and Genomics of Drug Sensitivity in Cancer (GDSC) for TNBC cell lines, along with drug perturbation information from Connectivity Map (CMap). In the TCGA-TNBC cohort, higher PPAR signaling activity was not associated with clinical stage, prognosis, tumor mutational burden, microsatellite instability, homologous recombination deficiency, stemness, or proliferation status. However, it was linked to older age; an elevated rate of piccolo presynaptic cytomatrix protein (PCLO) mutations; and oncogenic signal transduction involving MAPK, Ras, and PI3K-Akt pathways. Additionally, it influenced biological pathways including fatty acid metabolism, AMPK signaling, and ferroptosis. Strikingly, higher PPAR activity appeared to promote the formation of an antitumor immune and microbial microenvironment. In the GDSC-TNBC cells, nevertheless, it seemed to incur chemoresistance. Furthermore, we identified a batch of potential compounds that can regulate the PPAR signaling pathway. Lastly, our experimental validation demonstrated the ability of the histone deacetylase (HDAC) inhibitor chidamide to activate the PPAR signal in TNBC cells. In conclusion, the PPAR signaling pathway likely has pleiotropic biological effects in TNBC. These preliminary but interesting findings enhance our understanding of the role played by PPAR signal and provide new insights into the heterogeneity driven by it in TNBC.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2024 ","pages":"4164906"},"PeriodicalIF":3.5,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mangiferin and EGCG Compounds Fight Against Hyperlipidemia by Promoting FFA Oxidation via AMPK/PPAR<i>α</i>.","authors":"Yahui Xu, Jie Zhang, Ting Zhang, Minghui Zi, Qiao Zhang","doi":"10.1155/ppar/7178801","DOIUrl":"10.1155/ppar/7178801","url":null,"abstract":"<p><p><b>Background:</b> Hyperlipidemia is a critical risk factor for obesity, diabetes, cardiovascular diseases, and other chronic diseases. Our study was to determine the effects and mechanism of mangiferin (MF) and epigallocatechin gallate (EGCG) compounds on improving hyperlipidemia in HepG2 cells. <b>Methods:</b> HepG2 cells were treated with 0.25 mM palmitic acid (PA) and then incubated with MF (12.5, 25, and 50 <i>μ</i>M) or EGCG (25, 50, and 100 <i>μ</i>M) or MF:EGCG (0:0, 6.25:12.5, 25:50, and 50:100 <i>μ</i>M:<i>μ</i>M) for 24 h. The improvement of hyperlipidemia was verified by Oil Red O staining, changes in triglyceride (TG) and free fatty acid (FFA) levels, and the expression of lipid metabolizing proteins in western blotting. <b>Results:</b> MF (12.5, 25, and 50 <i>μ</i>M) or EGCG (25, 50, and 100 <i>μ</i>M) markedly lowered lipid accumulations by lipid index levels. Furthermore, we found that the optimum concentration of MF and EGCG compounds was 25:50 (<i>μ</i>M:<i>μ</i>M), which significantly reduced the FFA level, TG, and total cholesterol (TC) accumulations and increased FFA uptake in HepG2 cells, and the effect was better than that of single phytochemicals. The adenosine 5⁣'-monophosphate (AMP)-activated protein kinase (AMPK) protein and its downstream proteins sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor <i>α</i> (PPAR<i>α</i>), and those involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) were also markedly increased in HepG2 cells. The upregulation of protein expression was reversed when AMPK-specific inhibitor Compound C was added. <b>Conclusions:</b> MF and EGCG (25:50 <i>μ</i>M) compounds protect against hyperlipidemia by promoting the FFA oxidation, alleviating TG and TC accumulations via the AMPK/PPAR<i>α</i> pathway in PA-treated HepG2 cells.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2024 ","pages":"7178801"},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11679271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic and Lung Inflammation and Oxidative Stress Associated With Behavioral Changes Induced by Inhaled Paraquat Are Ameliorated by Carvacrol.","authors":"Arghavan Memarzia, Fatemeh Amin, Amin Mokhtari-Zaer, Zohre Arab, Saeideh Saadat, Mahrokh Heydari, Zahra Ghasemi, Farzaneh Naghdi, Mahmoud Hosseini, Mohammad Hossein Boskabady","doi":"10.1155/2024/4049448","DOIUrl":"10.1155/2024/4049448","url":null,"abstract":"<p><p>Paraquat (PQ) is an herbicide toxin that induces injury in different organs. The anti-inflammatory and antioxidant effects of carvacrol were reported previously. The effects of carvacrol and pioglitazone (Pio) alone and their combination on inhaled PQ-induced systemic and lung oxidative stress and inflammation as well as behavioral changes were examined in rats. In this study, animals were exposed to saline (control [Ctrl]) or PQ (PQ groups) aerosols. PQ-exposed animals were treated with 0.03 mg/kg/day dexamethasone (Dexa), 20 and 80 mg/kg/day carvacrol (C-L and C-H), 5 mg/kg/day Pio, and Pio+C-L for 16 days. Inhaled PQ markedly enhanced total and differential white blood cell (WBC) counts, nitric oxide (NO), and malondialdehyde (MDA) levels but decreased catalase (CAT) and superoxide dismutase (SOD) activities and thiol levels both in the bronchoalveolar lavage fluid (BALF) and blood and increased interferon-gamma (INF-<i>γ</i>) and interleukin-10 (IL-10) levels in the BALF (<i>p</i> < 0.001 for all cases) except lymphocyte count in blood which was not significantly changed. The escape latency and traveled distance were increased in the PQ group. However, the time spent in the target quadrant in the Morris water maze (MWM) test and the duration of time latency in the dark room in the shuttle box test were reduced after receiving an electrical shock (<i>p</i> < 0.05-<i>p</i> < 0.001). Inhaled PQ-induced changes were significantly improved in carvacrol, Pio, Dexa, and especially in the combination of the Pio+C-L treated groups (<i>p</i> < 0.05-<i>p</i> < 0.001). Carvacrol and Pio improved PQ-induced changes similar to Dexa, but ameliorative effects produced by combination treatments of Pio+C-L were more prominent than Pio and C-L alone, suggesting a potentiating effect for the combination of the two agents.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2024 ","pages":"4049448"},"PeriodicalIF":3.5,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared Mechanisms in <i>Pparγ1sv</i> and <i>Pparγ2</i> Expression in 3T3-L1 Cells: Studies on Epigenetic and Positive Feedback Regulation of <i>Pparγ</i> during Adipogenesis.","authors":"Yasuhiro Takenaka, Yoshihiko Kakinuma, Masaaki Ikeda, Ikuo Inoue","doi":"10.1155/2024/5518933","DOIUrl":"10.1155/2024/5518933","url":null,"abstract":"<p><p>We have previously reported the identification of a novel splicing variant of the mouse peroxisome proliferator-activated receptor-<i>γ</i> (<i>Pparγ</i>), referred to as <i>Pparγ1sv</i>. This variant, encoding the PPAR<i>γ</i>1 protein, is abundantly and ubiquitously expressed, playing a crucial role in adipogenesis. <i>Pparγ1sv</i> possesses a unique promoter and 5' untranslated region (5'UTR), distinct from those of the canonical mouse <i>Pparγ1</i> and <i>Pparγ2</i> mRNAs. We observed a significant increase in DNA methylation at two CpG sites within the proximal promoter region (-733 to -76) of <i>Pparγ1sv</i> during adipocyte differentiation. Concurrently, chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) using antibodies against H3K4me3 and H3K27ac indicated marked elevations in both methylation and acetylation of histone H3, while the repressive histone mark H3K9me2 significantly decreased, at the transcription start sites of both <i>Pparγ1sv</i> and <i>Pparγ2</i> following differentiation. Knocking down <i>Pparγ1sv</i> using specific siRNA also led to a decrease in <i>Pparγ2</i> mRNA and PPAR<i>γ</i>2 protein levels; conversely, knocking down <i>Pparγ2</i> resulted in reduced <i>Pparγ1sv</i> mRNA and PPAR<i>γ</i>1 protein levels, suggesting synergistic transcriptional regulation of <i>Pparγ1sv</i> and <i>Pparγ2</i> during adipogenesis. Furthermore, our experiments utilizing the CRISPR-Cas9 system identified crucial PPAR<i>γ</i>-binding sites within the <i>Pparγ</i> gene locus, underscoring their significance in adipogenesis. Based on these findings, we propose a model of positive feedback regulation for <i>Pparγ1sv</i> and <i>Pparγ2</i> expression during the adipocyte differentiation process in 3T3-L1 cells.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2024 ","pages":"5518933"},"PeriodicalIF":3.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between Nuclear Receptor and Alpha-Adrenergic Agonist Subtypes in Metabolism and Systemic Hemodynamics of Spontaneously Hypertensive Rats.","authors":"Sheryar Afzal, Munavvar Abdul Sattar, Ibrahim Albokhadaim, Ali Attiq, Mahmoud Kandeel, Aimi Syamima Abdul Manap, Sameer M Alhojaily","doi":"10.1155/2024/5868010","DOIUrl":"10.1155/2024/5868010","url":null,"abstract":"<p><p>Partial and full PPAR-<i>γ</i> agonists have shown promising effects and antihypertensive and antidiabetic agents through increased plasma adiponectin concentration. This study is aimed at examining the role of PPAR-<i>γ</i>, alpha-adrenoceptors, and adiponectin receptors in the modulation of vasopressor responses to angiotensin II (Ang II) and adrenergic agonists, after a subset treatment of partial and full PPAR-<i>γ</i> agonists, each individually, and also when coupled with adiponectin in SHRs. The antioxidant potential and metabolic indices for these animals were also determined. Group I (WKY) and group II (SHR) were designated as normotensive control and hypertensive control, respectively. Groups III (SHR) and IV (SHR) received irbesartan (30 mg/kg) and pioglitazone (10 mg/kg) orally for 28 days, and groups V (SHR), VI (SHR), and VII (SHR) were treated with adiponectin (2.5 <i>μ</i>g/kg) intraperitoneally alone, in combination with irbesartan, and in combination with pioglitazone, respectively, from days 21 to 28 only. On day 29, sodium pentobarbitone (60 mg/kg) was used to anesthetize all test animals, and systemic hemodynamic and plasma adiponectin concentrations and <i>in vitro</i> and <i>in vivo</i> antioxidant potential were measured. As compared to the WKY control, the SHR control group's noninvasive blood pressure and basal mean arterial pressure were significantly greater, along with increased arterial stiffness, lower plasma nitric oxide, adiponectin concentration, and antioxidant enzyme levels (all <i>P</i> < 0.05). However, they were gradually normalized by single drug treatments in all groups, and to a greater extent in the SHR + Irb + Adp group (<i>P</i> < 0.05). In the acute study, the dose dependant mean arterial pressure responses to intravenously administered adrenergic agonists and angiotensin-II were significantly larger in SHRs as compared to WKY by 20-25%. Adiponectin alone and in combination significantly blunted vasopressor responses to these alpha-adrenergic agonists in the SHR + Pio + Adp group by 63%, whereas attenuated responses to ANG-II administration to 70% in SHR + Irb + Adp. In conclusion, the combined treatment of adiponectin with PPAR-agonists reduced the systemic vascular responses to adrenergic agonists and improved arterial stiffness. This an evidence of the interaction of adiponectin receptors, PPAR-<i>γ</i>, alpha-adrenoceptors, and ANG-II in the systemic vasculature of SHRs. A significant level of synergism has also been proved among full PPAR-<i>γ</i> agonists and adiponectin receptors.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2024 ","pages":"5868010"},"PeriodicalIF":3.5,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma","authors":"Boxuan Han, Jiaming Chen, Shaoshi Chen, Xixi Shen, Lizhen Hou, Jugao Fang, Meng Lian","doi":"10.1155/2024/2271214","DOIUrl":"https://doi.org/10.1155/2024/2271214","url":null,"abstract":"It has been demonstrated that PPARG may interact with the PTEN-PI3K/AKT pathway, contributing to its involvement in the chemotherapy treatment of hypopharyngeal squamous cell carcinoma (HSCC). However, the underlying mechanism remains largely unknown. In this study, gene expression profiles of 17 HSCC patients, comprising 8 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP), were collected and analyzed to investigate expression patterns, correlations, influencing factors of the PPARG-PTEN-PI3K/AKT pathway, and its role in regulating chemosensitivity. The results revealed significantly increased expression (&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;)&lt;/span&gt;&lt;/span&gt; of AKT1, AKT2, AKT3, PIK3CA, PPARG, and PTEN in the CSP group compared to the CNSP group. Specifically, AKT2 exhibited significant overexpression in tumor tissue (&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-113\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,11.342,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;&lt;span&gt;&lt;/span&gt;&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"22.555183800000002 -8.34882 21.921 11.7782\" width=\"21.921pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,22.605,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,28.845,0)\"&gt;&lt;use xlink:href=\"#g113-47\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,31.809,0)\"&gt;&lt;use xlink:href=\"#g113-49\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,38.049,0)\"&gt;&lt;/path&gt;&lt;/g&gt;&lt;/svg&gt;),&lt;/span&gt;&lt;/span&gt; while AKT2, AKT3, PPARG, and PTEN displayed significant increases in normal tissue (&lt;span&gt;&lt;svg height=\"11.7782pt\" style=\"vertical-align:-3.42938pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 18.973 11.7782\" width=\"18.973pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;g transform=\"matrix(.013,0,0,-0.013,0,0)\"&gt;&lt;use xlink:href=\"#g113-113\"&gt;&lt;/use&gt;&lt;/g&gt;&lt;g tr","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"3 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140099318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxisome Proliferator-Activated Receptor γ Regulates Lipid Metabolism in Sheep Trophoblast Cells through mTOR Pathway-Mediated Autophagy","authors":"Kexing Hao, Jing Wang, Hengbin Yu, Lei Chen, Weibin Zeng, Zhengrong Wang, Guangdong Hu","doi":"10.1155/2023/6422804","DOIUrl":"https://doi.org/10.1155/2023/6422804","url":null,"abstract":"Peroxisome proliferator-activated receptor gamma (PPARγ) is a key nuclear receptor transcription factor that is highly expressed in trophoblastic cells during embryonic attachment and is accompanied by rapid cell proliferation and increased lipid accumulation. We previously showed that the autophagy pathway is activated in cells after activation of PPARγ, accompanied by increased lipid accumulation. In this study, we used PPARγ agonist rosiglitazone and inhibitor GW9662, as well as autophagy activator rapamycin and inhibitor 3-methyladenine, to unravel the probable mechanism of PPARγ engaged in lipid metabolism in sheep trophoblast cells (STCs). After 12 h, 24 h, and 48 h of drug treatment, the levels of autophagy-related proteins were detected by Western blot, the triglyceride content and MDA level of cells were detected by colorimetry, and the lipid droplets and lysosomes were localized by immunofluorescence. We found that PPARγ inhibited the activity of mammalian target of rapamycin (mTOR) pathway in STCs for a certain period of time, promoted the increase of autophagy and lysosome formation, and enhanced the accumulation of lipid droplets and triglycerides. Compared with cells whose PPARγ function is activated, blocking autophagy before activating PPARγ will hinder lipid accumulation in STCs. Pretreatment of cells with rapamycin promoted autophagy with results similar to rosiglitazone treatment, while inhibition of autophagy with 3-methyladenine reduced lysosome and lipid accumulation. Based on these observations, we conclude that PPARγ can induce autophagy by blocking the mTOR pathway, thereby promoting the accumulation of lipid droplets and lysosomal degradation, providing an energy basis for the rapid proliferation of trophoblast cells during embryo implantation. In brief, this study partially revealed the molecular regulatory mechanism of PPARγ, mTOR pathway, and autophagy on trophoblast cell lipid metabolism, which provides a theoretical basis for further exploring the functional regulatory network of trophoblast cells during the attachment of sheep embryos.","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" 34","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135340502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of PPARG in Chemosensitivity-Regulating Network for Hypopharyngeal Squamous Cell Carcinoma.","authors":"Fanyong Kong,&nbsp;Boxuan Han,&nbsp;Jiaming Chen,&nbsp;Xixi Shen,&nbsp;Lizhen Hou,&nbsp;Jugao Fang,&nbsp;Meng Lian","doi":"10.1155/2023/6019318","DOIUrl":"https://doi.org/10.1155/2023/6019318","url":null,"abstract":"<p><p>PPARG has been reported to promote chemosensitivity in hypopharyngeal squamous cell carcinoma (HSCC). However, few studies tested its significance in the texture of a complex molecular network regulating chemosensitivity in HSCC. Here, we first employed RNA expression data analysis and literature data mining to uncover candidate genes related to HSCC chemosensitivity. Then, we constructed the molecular network regulating chemosensitivity in HSCC. After that, we employed degree centrality (DC) and weighted centrality (WC) to test the significance of PPARG within the regulating network. Pathway enrichment was done to study the cofunctions of PPARG and the rest of the genes within the network. The findings of our study contribute to the construction of a comprehensive network that regulates HSCC chemosensitivity, consisting of 57 genes, including PPARG. Notably, within this network, PPARG demonstrates a ranking of #5 and #13 based on DC and WC, respectively. Moreover, PPARG is connected to 29 out of the 57 genes and plays roles in multiple functional groups. These top related genes include AKT1, TP53, PTEN, MAPK1, NOTCH1, BECN1, PTGS2, SPP1, and RAC1. PPARG gets enriched in several key functional groups that have been implicated in the regulation of chemosensitivity, including those associated with the response to nutrients, vitamins, and peptides, the cellular response to chemical stress, and the regulation of hormone secretion and growth. Our results emphasize the involvement of PPARG and its interconnectedness with other genes in the regulation of HSCC chemosensitivity.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"6019318"},"PeriodicalIF":2.9,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41145713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis Identifies the PPAR-Targeted Genes Associated with Ovarian Cancer Prognosis and Tumor Microenvironment.","authors":"Xiao-Fei Leng,&nbsp;Gao-Fa Wang,&nbsp;Hao Yin,&nbsp;Feng Wei,&nbsp;Kang-Kang Zeng,&nbsp;Yi-Qun Zhang","doi":"10.1155/2023/6637414","DOIUrl":"https://doi.org/10.1155/2023/6637414","url":null,"abstract":"<p><strong>Background: </strong>There is a significant role for peroxisome proliferator-activated receptors (PPARs) in the development of cancer. Nevertheless, the role of PPARs-related genes in ovarian cancer (OC) remains unclear.</p><p><strong>Methods: </strong>The open-accessed data used for analysis were downloaded from The Cancer Genome Atlas database, which was analyzed using the R software.</p><p><strong>Results: </strong>In our study, we comprehensively investigated the PPAR target genes in OC, including their biological role. Meanwhile, a prognosis signature consisting of eight PPAR target genes was established, including apolipoprotein A-V, UDP glucuronosyltransferase 2 family, polypeptide B4, TSC22 domain family, member 1, growth hormone inducible transmembrane protein, renin, dedicator of cytokinesis 4, enoyl CoA hydratase 1, peroxisomal (ECH1), and angiopoietin-like 4, which showed a good prediction efficiency. A nomogram was constructed by combining the clinical feature and risk score. Immune infiltration and biological enrichment analysis were applied to investigate the difference between high- and low-risk patients. Immunotherapy analysis indicated that low-risk patients might respond better to immunotherapy. Drug sensitivity analysis indicated that high-risk patients might respond better to bleomycin, nilotinib, pazopanib, pyrimethamine, and vinorelbine, yet worse to cisplatin and gefitinib. Furthermore, the gene ECH1 was selected for further analysis.</p><p><strong>Conclusions: </strong>Our study identified a prognosis signature that could effectively indicates patients survival. Meanwhile, our study can provide the direction for future studies focused on the PPARs in OC.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"6637414"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significance of PPARA as a Treatment Target for Chronic Lymphocytic Leukemia.","authors":"Xixi Xiang,&nbsp;Fu Li,&nbsp;Sha Zhou,&nbsp;Yunjing Zeng,&nbsp;Xiaojuan Deng,&nbsp;Hongyang Zhang,&nbsp;Jiali Li,&nbsp;Hongyun Liu,&nbsp;Jun Rao,&nbsp;Lei Gao,&nbsp;Cheng Zhang,&nbsp;Qin Wen,&nbsp;Li Gao,&nbsp;Xi Zhang","doi":"10.1155/2023/8456833","DOIUrl":"https://doi.org/10.1155/2023/8456833","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptor alpha (PPARA) has been suggested as a therapeutic target for chronic lymphocytic leukemia (CLL). However, the underlying molecular mechanism remains largely unclear. In this study, we analyzed DNA next-generation sequencing (NGS) data and clinical information from 86 CLL patients to identify gene markers related to treatment-free survival (TFS) length. We then constructed a genetic network that includes CLL promoters, treatment targets, and TFS-related marker genes. To assess the significance of PPARA within the network, we utilized degree centrality (DC) and pathway enrichment score (EScore). Clinical and NGS data revealed 10 TFS length-related gene markers, including RPS15, FOXO1, FBXW7, KMT2A, NOTCH1, GNA12, EGR2, GNA13, KDM6A, and ATM. Through literature data mining, 83 genes were identified as CLL upstream promoters and treatment targets. Among them, PPARA exhibited a stronger connection to CLL and TFS-related gene markers, as evidenced by its ranking at No. 13 based on DC, compared to most of the other promoters (>84%). Additionally, PPARA co-functions with 70 out of 92 in-network genes in various functional pathways/gene groups related to CLL pathology, such as regulation of cell adhesion, inflammation, reactive oxygen species, and cell differentiation. Based on our findings, PPARA is considered one of the critical genes within a large genetic network that influences the prognosis and TFS of CLL through multiple pathogenic pathways.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"8456833"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10317583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9802598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}