PPAR Research最新文献

{"title":"<i>Nuclear Protein 1</i> Expression Is Associated with PPARG in Bladder Transitional Cell Carcinoma.","authors":"Chao Lu,&nbsp;Shenglin Gao,&nbsp;Li Zhang,&nbsp;Xiaokai Shi,&nbsp;Yin Chen,&nbsp;Shuzhang Wei,&nbsp;Li Zuo,&nbsp;Lifeng Zhang","doi":"10.1155/2023/6797694","DOIUrl":"https://doi.org/10.1155/2023/6797694","url":null,"abstract":"<p><strong>Background: </strong>The <i>Nuclear protein 1</i> gene was first discovered in acute pancreatitis and functions as an oncogene in cancer progression and drug resistance. However, the role of <i>Nuclear protein 1</i> in bladder transitional cell carcinoma (BTCC) is still unclear.</p><p><strong>Methods: </strong>The Cancer Genome Atlas database and immunohistochemical analysis were adopted to evaluate <i>Nuclear protein 1</i> expression in BTCC. We applied lentivirus-mediated small-interfering RNA to down-regulate the expression of <i>Nuclear protein 1</i> in BTCC cell lines. We further performed an Affymetrix microarray and Gene Set Enrichment Analysis (GSEA) to assess the genes and signaling pathways related to <i>Nuclear protein 1</i>.</p><p><strong>Results: </strong>We found that <i>Nuclear protein 1</i> expression was up-regulated in BTCC and positively related to the degree of BTCC malignancy. Compared with Caucasian patients with BTCC, <i>Nuclear protein 1</i> expression was attenuated in Asian patients. The Affymetrix microarray showed that lipopolysaccharide was the upstream regulatory factor of <i>Nuclear protein 1</i> in BTCC. The GSEA indicated that <i>Nuclear protein 1</i> expression was associated with signaling pathways in cancer, peroxisome proliferator-activated receptor (PPAR) pathways, and RNA degradation. The expression of <i>Nuclear protein 1</i> was negatively correlated with PPARG (<i>R</i> = -0.290, <i>P</i> < 0.001), but not with PPARA (<i>R</i> = 0.047, <i>P</i> = 0.344) and PPARD (<i>R</i> = -0.055, <i>P</i> = 0.260).</p><p><strong>Conclusions: </strong>The study findings indicate that <i>Nuclear protein 1</i> is positively associated with the malignancy degree of BTCC and that <i>Nuclear protein 1</i> expression is negatively correlated with PPARG.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"6797694"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487460","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":"Vitamin A: A Key Inhibitor of Adipocyte Differentiation.","authors":"Manal A Malibary","doi":"10.1155/2023/7405954","DOIUrl":"https://doi.org/10.1155/2023/7405954","url":null,"abstract":"<p><p>Inhibiting adipocyte differentiation, the conversion of preadipocytes to mature functional adipocytes, might represent a new approach to treating obesity and related metabolic disorders. Peroxisome proliferator-activated receptor <i>γ</i> and CCAAT-enhancer-binding protein <i>α</i> are two master coregulators controlling adipogenesis both in culture and in vivo. Many recent studies have confirmed the relationship between retinoic acid (RA) and the conversion of embryonic stem cells into adipocytes; however, these studies have shown that RA potently blocks the differentiation of preadipocytes into mature adipocytes. Nevertheless, the functional role of RA in early tissue development and stem cell differentiation, including in adipose tissue, remains unclear. This study highlights transcription factors that block adipocyte differentiation and maintain preadipocyte status, focusing on those controlled by RA. However, some of these novel adipogenesis inhibitors have not been validated in vivo, and their mechanisms of action require further clarification.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"7405954"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10707322","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":"Appraisal of the Possible Role of PPAR<i>γ</i> Upregulation by CLA of Probiotic <i>Pediococcus pentosaceus</i> GS4 in Colon Cancer Mitigation.","authors":"Vinay Dubey,&nbsp;Alok Kumar Mishra,&nbsp;Asit Ranjan Ghosh","doi":"10.1155/2023/9458308","DOIUrl":"https://doi.org/10.1155/2023/9458308","url":null,"abstract":"<p><p>The prevalence of colon cancer (CC) is increasing at the endemic scale, which is accompanied by subsequent morbidity and mortality. Although there have been noteworthy achievements in the therapeutic strategies in recent years, the treatment of patients with CC remains a formidable task. The current study focused on to study role of biohydrogenation-derived conjugated linoleic acid (CLA) of probiotic <i>Pediococcus pentosaceus</i> GS4 (CLA_GS4) against CC, which induced peroxisome proliferator-activated receptor gamma (PPAR<i>γ</i>) expression in human CC HCT-116 cells. Pre-treatment with PPAR<i>γ</i> antagonist bisphenol A diglycidyl ether has significantly reduced the inhibitory efficacy of enhanced cell viability of HCT-116 cells, suggesting the PPAR<i>γ</i>-dependent cell death. The cancer cells treated with CLA/CLA_GS4 demonstrated the reduced level of Prostaglandin E2 PGE₂ in association with reduced COX-2 and 5-LOX expressions. Moreover, these consequences were found to be associated with PPAR<i>γ</i>-dependent. Furthermore, delineation of mitochondrial dependent apoptosis with the help of molecular docking LigPlot analysis showed that CLA can bind with hexokinase-II (hHK-II) (highly expressed in cancer cells) and that this association underlies voltage dependent anionic channel to open, thereby causing mitochondrial membrane depolarization, a condition that initiates intrinsic apoptotic events. Apoptosis was further confirmed by annexin V staining and elevation of caspase 1p10 expression. Taken all together, it is deduced that, mechanistically, the upregulation of PPAR<i>γ</i> by CLA_GS4 of <i>P</i>. <i>pentosaceus</i> GS4 can alter cancer cell metabolism in association with triggering apoptosis in CC.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2023 ","pages":"9458308"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10854739","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":"Activation of PPAR<i>γ</i> Protects Obese Mice from Acute Lung Injury by Inhibiting Endoplasmic Reticulum Stress and Promoting Mitochondrial Biogenesis.","authors":"Yin Tang,&nbsp;Ke Wei,&nbsp;Ling Liu,&nbsp;Jingyue Ma,&nbsp;Siqi Wu,&nbsp;Wenjing Tang","doi":"10.1155/2022/7888937","DOIUrl":"https://doi.org/10.1155/2022/7888937","url":null,"abstract":"<p><strong>Objective: </strong>Obesity-induced endoplasmic reticulum (ER) stress plays a role in increased susceptibility to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The activation of peroxisome proliferator-activated receptor-<i>γ</i> (PPAR<i>γ</i>) is associated with lung protection and is effective in ameliorating ER stress and mitochondrial dysfunction. The aim of this study was to investigate the expression of PPAR<i>γ</i> in the lung tissues of obese mice and explore whether the PPAR<i>γ</i>-dependent pathway could mediate decreased ALI/ARDS by regulating ER stress and mitochondrial biogenesis.</p><p><strong>Methods: </strong>We determined PPAR<i>γ</i> expression in the lung tissues of normal and obese mice. ALI models of alveolar epithelial cells and of obese mice were used and treated with either PPAR<i>γ</i> activator rosiglitazone (RSG) or PPAR<i>γ</i> inhibitor GW9662. Lung tissue and cell samples were collected to assess lung inflammation and apoptosis, and ER stress and mitochondrial biogenesis were detected.</p><p><strong>Results: </strong>PPAR<i>γ</i> expression was significantly decreased in the lung tissue of obese mice compared with that in normal mice. Both in vivo and in vitro studies have shown that activation of PPAR<i>γ</i> leads to reduced expression of the ER stress marker proteins 78-kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and Caspase12. Conversely, expression of the mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor <i>γ</i> coactivator 1 (PGC-1<i>α</i>), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) increased. Furthermore, activation of PPAR<i>γ</i> is associated with decreased levels of lung inflammation and epithelial apoptosis and increased expression of adiponectin (APN) and mitofusin2 (MFN2). GW9662 bound to PPAR<i>γ</i> and blocked its transcriptional activity and then diminished the protective effect of PPAR<i>γ</i> on lung tissues.</p><p><strong>Conclusions: </strong>PPAR<i>γ</i> activation exerts anti-inflammation effects in alveolar epithelia by alleviating ER stress and promoting mitochondrial biogenesis. Therefore, lower levels of PPAR<i>γ</i> in the lung tissues of obese mice may lead to an increased susceptibility to ALI.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2022 ","pages":"7888937"},"PeriodicalIF":2.9,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33497358","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":"Noncoding RNAs Associated with PPARs in Etiology of MAFLD as a Novel Approach for Therapeutics Targets.","authors":"Fatemeh Kazeminasab,&nbsp;Maryam Baharlooie,&nbsp;Kamran Ghaedi","doi":"10.1155/2022/6161694","DOIUrl":"https://doi.org/10.1155/2022/6161694","url":null,"abstract":"<p><strong>Background: </strong>Metabolic associated fatty liver disease (MAFLD) is a complex disease that results from the accumulation of fat in the liver. MAFLD is directly associated with obesity, insulin resistance, diabetes, and metabolic syndrome. PPAR<i>γ</i> ligands, including pioglitazone, are also used in the management of this disease. Noncoding RNAs play a critical role in various diseases such as diabetes, obesity, and liver diseases including MAFLD. However, there is no adequate knowledge about the translation of using these ncRNAs to the clinics, particularly in MAFLD conditions. The aim of this study was to identify ncRNAs in the etiology of MAFLD as a novel approach to the therapeutic targets.</p><p><strong>Methods: </strong>We collected human and mouse MAFLD gene expression datasets available in GEO. We performed pathway enrichment analysis of total mRNAs based on KEGG repository data to screen the most potential pathways in the liver of MAFLD human subjects and mice model, and analyzed pathway interconnections via ClueGO. Finally, we screened disease causality of the MAFLD ncRNAs, which were associated with PPARs, and then discussed the role of revealed ncRNAs in PPAR signaling and MAFLD.</p><p><strong>Results: </strong>We found 127 ncRNAs in MAFLD which 25 out of them were strongly validated before for regulation of PPARs. With a polypharmacology approach, we screened 51 ncRNAs which were causal to a subset of diseases related to MAFLD.</p><p><strong>Conclusion: </strong>This study revealed a subset of ncRNAs that could help in more clear and guided designation of preclinical and clinical studies to verify the therapeutic application of the revealed ncRNAs by manipulating the PPARs molecular mechanism in MAFLD.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"6161694"},"PeriodicalIF":2.9,"publicationDate":"2022-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40373606","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":"Impact of Phytochemicals on PPAR Receptors: Implications for Disease Treatments.","authors":"Ayesheh Enayati, Mobina Ghojoghnejad, Basil D Roufogalis, Seyed Adel Maollem, Amirhossein Sahebkar","doi":"10.1155/2022/4714914","DOIUrl":"10.1155/2022/4714914","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptors (PPARs) are members of the ligand-dependent nuclear receptor family. PPARs have attracted wide attention as pharmacologic mediators to manage multiple diseases and their underlying signaling targets. They mediate a broad range of specific biological activities and multiple organ toxicity, including cellular differentiation, metabolic syndrome, cancer, atherosclerosis, neurodegeneration, cardiovascular diseases, and inflammation related to their up/downstream signaling pathways. Consequently, several types of selective PPAR ligands, such as fibrates and thiazolidinediones (TZDs), have been approved as their pharmacological agonists. Despite these advances, the use of PPAR agonists is known to cause adverse effects in various systems. Conversely, some naturally occurring PPAR agonists, including polyunsaturated fatty acids and natural endogenous PPAR agonists curcumin and resveratrol, have been introduced as safe agonists as a result of their clinical evidence or preclinical experiments. This review focuses on research on plant-derived active ingredients (natural phytochemicals) as potential safe and promising PPAR agonists. Moreover, it provides a comprehensive review and critique of the role of phytochemicals in PPARs-related diseases and provides an understanding of phytochemical-mediated PPAR-dependent and -independent cascades. The findings of this research will help to define the functions of phytochemicals as potent PPAR pharmacological agonists in underlying disease mechanisms and their related complications.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2022 ","pages":"4714914"},"PeriodicalIF":3.5,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9453090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33460905","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":"GaitRec-Net: A Deep Neural Network for Gait Disorder Detection Using Ground Reaction Force.","authors":"Chandrasen Pandey,&nbsp;Diptendu Sinha Roy,&nbsp;Ramesh Chandra Poonia,&nbsp;Ayman Altameem,&nbsp;Soumya Ranjan Nayak,&nbsp;Amit Verma,&nbsp;Abdul Khader Jilani Saudagar","doi":"10.1155/2022/9355015","DOIUrl":"https://doi.org/10.1155/2022/9355015","url":null,"abstract":"<p><p>Walking (gait) irregularities and abnormalities are predictors and symptoms of disorder and disability. In the past, elaborate video (camera-based) systems, pressure mats, or a mix of the two has been used in clinical settings to monitor and evaluate gait. This article presents an artificial intelligence-based comprehensive investigation of ground reaction force (GRF) pattern to classify the healthy control and gait disorders using the large-scale ground reaction force. The used dataset comprised GRF measurements from different patients. The article includes machine learning- and deep learning-based models to classify healthy and gait disorder patients using ground reaction force. A deep learning-based architecture GaitRec-Net is proposed for this classification. The classification results were evaluated using various metrics, and each experiment was analysed using a fivefold cross-validation approach. Compared to machine learning classifiers, the proposed deep learning model is found better for feature extraction resulting in high accuracy of classification. As a result, the proposed framework presents a promising step in the direction of automatic categorization of abnormal gait pattern.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"9355015"},"PeriodicalIF":2.9,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40335979","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":"Luteolin Pretreatment Attenuates Hepatic Ischemia-Reperfusion Injury in Mice by Inhibiting Inflammation, Autophagy, and Apoptosis via the ERK/PPAR<i>α</i> Pathway.","authors":"Yuhui Jiang,&nbsp;Wenjuan Yang,&nbsp;Jiameng Ding,&nbsp;Jie Ji,&nbsp;Liwei Wu,&nbsp;Yuanyuan Zheng,&nbsp;Yan Li,&nbsp;Ziqi Cheng,&nbsp;Jie Zhang,&nbsp;Qiang Yu,&nbsp;Jiao Feng,&nbsp;Jingjing Li,&nbsp;Jianye Wu,&nbsp;Yingqun Zhou,&nbsp;Chuanyong Guo","doi":"10.1155/2022/8161946","DOIUrl":"https://doi.org/10.1155/2022/8161946","url":null,"abstract":"<p><p>Hepatic ischemia-reperfusion (IR) injury is a clinically significant process that frequently occurs in liver transplantation, partial hepatectomy, and hemorrhagic shock. The aim of this study was to explore the effectiveness of luteolin in hepatic IR injury and the underlying mechanism. BALB/c mice were randomly divided into six groups, including normal controls (NC), luteolin (50 mg/kg), sham procedure, IR+25 mg/kg luteolin, and IR+50 mg/kg luteolin group. Serum and tissue samples were collected at 6 and 24 h after reperfusion to assay liver enzymes, inflammatory factors, expression of proteins associated with apoptosis and autophagy, and factors associated with the extracellular signal-regulated kinase/peroxisome proliferator-activated receptor alpha (ERK/PPAR<i>α</i>) pathway. Luteolin preconditioning decreased hepatocyte injury caused by ischemia-reperfusion, downregulated inflammatory factors, and inhibited apoptosis and autophagy. Luteolin also inhibited ERK phosphorylation and activated PPAR<i>α</i>.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"8161946"},"PeriodicalIF":2.9,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40697397","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":"Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models.","authors":"Ali Mahmoudi,&nbsp;Seyed Adel Moallem,&nbsp;Thomas P Johnston,&nbsp;Amirhossein Sahebkar","doi":"10.1155/2022/5805398","DOIUrl":"https://doi.org/10.1155/2022/5805398","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is initiated by excessive fat buildup in the liver, affecting around 35% of the world population. Various circumstances contribute to the initiation and progression of NAFLD, and it encompasses a wide range of disorders, from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Although several treatments have been proposed, there is no definitive cure for NAFLD. In recent decades, several medications related to other metabolic disorders have been evaluated in preclinical studies and in clinical trials due to the correlation of NAFLD with other metabolic diseases. Fenofibrate is a fibrate drug approved for dyslipidemia that could be used for modulation of hepatic fat accumulation, targeting peroxisome proliferator-activator receptors, and de novo lipogenesis. This drug offers potential therapeutic efficacy for NAFLD due to its capacity to decrease the accumulation of hepatic lipids, as well as its antioxidant, anti-inflammatory, and antifibrotic properties. To better elucidate the pathophysiological processes underlying NAFLD, as well as to test therapeutic agents/interventions, experimental animal models have been extensively used. In this article, we first reviewed experimental animal models that have been used to evaluate the protective effects of fenofibrate on NAFLD/NASH. Next, we investigated the impact of fenofibrate on the hepatic microcirculation in NAFLD and then summarized the beneficial effects of fenofibrate, as compared to other drugs, for the treatment of NAFLD. Lastly, we discuss possible adverse side effects of fenofibrate on the liver.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":"5805398"},"PeriodicalIF":2.9,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40400776","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":"PPAR-γ Agonist Pioglitazone Restored Mouse Liver mRNA Expression of Clock Genes and Inflammation-Related Genes Disrupted by Reversed Feeding","authors":"T. Fedchenko, O. Izmailova, V. Shynkevych, O. Shlykova, I. Kaidashev","doi":"10.1155/2022/7537210","DOIUrl":"https://doi.org/10.1155/2022/7537210","url":null,"abstract":"Introduction The master clock, which is located in the suprachiasmatic nucleus (SCN), harmonizes clock genes present in the liver to synchronize life rhythms and bioactivity with the surrounding environment. The reversed feeding disrupts the expression of clock genes in the liver. Recently, a novel role of PPAR-γ as a regulator in correlating circadian rhythm and metabolism was demonstrated. This study examined the influence of PPAR-γ agonist pioglitazone (PG) on the mRNA expression profile of principle clock genes and inflammation-related genes in the mouse liver disrupted by reverse feeding. Methods Mice were randomly assigned to daytime-feeding and nighttime-feeding groups. Mice in daytime-feeding groups received food from 7 AM to 7 PM, and mice in nighttime-feeding groups received food from 7 PM to 7 AM. PG was administered in the dose of 20 mg/kg per os as aqueous suspension 40 μl at 7 AM or 7 PM. Each group consisted of 12 animals. On day 8 of the feeding intervention, mice were sacrificed by cervical dislocation at noon (05 hours after light onset (HALO)) and midnight (HALO 17). Liver expressions of Bmal1, Clock, Rev-erb alpha, Cry1, Cry2, Per1, Per2, Cxcl5, Nrf2, and Ppar-γ were determined by quantitative reverse transcription PCR. Liver expression of PPAR-γ, pNF-κB, and IL-6 was determined by Western blotting. Glucose, ceruloplasmin, total cholesterol, triglyceride concentrations, and ALT and AST activities were measured in sera by photometric methods. The null hypothesis tested was that PG and the time of its administration have no influence on the clock gene expression impaired by reverse feeding. Results Administration of PG at 7 AM to nighttime-feeding mice did not reveal any influence on the expression of the clock or inflammation-related genes either at midnight or at noon. In the daytime-feeding group, PG intake at 7 PM led to an increase in Per2 and Rev-erb alpha mRNA at noon, an increase in Ppar-γ mRNA at midnight, and a decrease in Nfκb (p65) mRNA at noon. In general, PG administration at 7 PM slightly normalized the impaired expression of clock genes and increased anti-inflammatory potency impaired by reversed feeding. This pattern was supported by biochemical substrate levels—glucose, total cholesterol, ALT, and AST activities. The decrease in NF-κB led to the inhibition of serum ceruloplasmin levels as well as IL-6 in liver tissue. According to our data, PG intake at 7 PM exerts strong normalization of clock gene expression with a further increase in Nrf2 and, especially, Ppar-γ and PPAR-γ expression with inhibition of Nfκb and pNF-κB expression in daytime-feeding mice. These expression changes resulted in decreased hyperglycemia, hypercholesterolemia, ALT, and AST activities. Thus, PG had a potent chronopharmacological effect when administered at 7 PM to daytime-feeding mice. Conclusions Our study indicates that reversed feeding induced the disruption of mouse liver circadian expression pattern of clock genes accompanied by","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48218991","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}