PPAR Research最新文献

{"title":"Stimulation of Alpha₁-Adrenergic Receptor Ameliorates Cellular Functions of Multiorgans beyond Vasomotion through PPAR<i>δ</i>.","authors":"Yong-Jik Lee,&nbsp;Hyun Soo Kim,&nbsp;Hong Seog Seo,&nbsp;Jin Oh Na,&nbsp;You-Na Jang,&nbsp;Yoon-Mi Han,&nbsp;Hyun-Min Kim","doi":"10.1155/2020/3785137","DOIUrl":"https://doi.org/10.1155/2020/3785137","url":null,"abstract":"<p><p>Cells can shift their metabolism between glycolysis and oxidative phosphorylation to enact their cell fate program in response to external signals. Widely distributed <i>α</i> ₁-adrenergic receptors (ARs) are physiologically stimulated during exercise, were reported to associate with the activating energetic AMPK pathway, and are expected to have biological effects beyond their hemodynamic effects. To investigate the effects and mechanism of AR stimulation on the physiology of the whole body, various <i>in vitro</i> and <i>in vivo</i> experiments were conducted using the AR agonist midodrine, 2-amino-<i>N</i>-[2-(2,5-dimethoxyphenyl)-2-hydroxy-ethyl]-acetamide. The expression of various biomarkers involved in ATP production was estimated through Western blotting, reverse transcription polymerase chain reaction, oxygen consumption rate, enzyme-linked immunosorbent assay (ELISA), fluorescence staining, and Oil red O staining in several cell lines (skeletal muscle, cardiac muscle, liver, macrophage, vascular endothelial, and adipose cells). In spontaneously hypertensive rats, blood pressure, blood analysis, organ-specific biomarkers, and general biomolecules related to ATP production were measured with Western blot analysis, immunohistochemistry, ELISA, and echocardiography. Pharmacological activation of <i>α</i> ₁-adrenergic receptors in C2C12 skeletal muscle cells promoted mitochondrial oxidative phosphorylation and ATP production by increasing the expression of catabolic molecules, including PPAR<i>δ</i>, AMPK, and PGC-1<i>α</i>, through cytosolic calcium signaling and increased GLUT4 expression, as seen in exercise. It also activated those energetic molecules and mitochondrial oxidative phosphorylation with cardiomyocytes, endothelial cells, adipocytes, macrophages, and hepatic cells and affected their relevant cell-specific biological functions. All of those effects occurred around 3 h (and peaked 6 h) after midodrine treatment. In spontaneously hypertensive rats, <i>α</i> ₁-adrenergic receptor stimulation affected mitochondrial oxidative phosphorylation and ATP production by activating PPAR<i>δ</i>, AMPK, and PGC-1<i>α</i> and the relevant biologic functions of multiple organs, suggesting organ crosstalk. The treatment lowered blood pressure, fat and body weight, cholesterol levels, and inflammatory activity; increased ATP content and insulin sensitivity in skeletal muscles; and increased cardiac contractile function without exercise training. These results suggest that the activation of <i>α</i> ₁-adrenergic receptor stimulates energetic reprogramming via PPAR<i>δ</i> that increases mitochondrial oxidative phosphorylation and has healthy and organ-specific biological effects in multiple organs, including skeletal muscle, beyond its vasomotion effect. In addition, the action mechanism of <i>α</i> ₁-adrenergic receptor may be mainly exerted via PPAR<i>δ</i>.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2020 ","pages":"3785137"},"PeriodicalIF":2.9,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/3785137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37677922","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":"Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma.","authors":"Oxana Yu Kytikova, Juliy M Perelman, Tatyana P Novgorodtseva, Yulia K Denisenko, Viktor P Kolosov, Marina V Antonyuk, Tatyana A Gvozdenko","doi":"10.1155/2020/8906968","DOIUrl":"10.1155/2020/8906968","url":null,"abstract":"<p><p>The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2020 ","pages":"8906968"},"PeriodicalIF":2.9,"publicationDate":"2020-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8906968","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37923569","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":"PPARs and the Development of Type 1 Diabetes.","authors":"Laurits J Holm,&nbsp;Mia Øgaard Mønsted,&nbsp;Martin Haupt-Jorgensen,&nbsp;Karsten Buschard","doi":"10.1155/2020/6198628","DOIUrl":"https://doi.org/10.1155/2020/6198628","url":null,"abstract":"<p><p>Peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors with a key role in glucose and lipid metabolism. PPARs are expressed in many cell types including pancreatic beta cells and immune cells, where they regulate insulin secretion and T cell differentiation, respectively. Moreover, various PPAR agonists prevent diabetes in the non-obese diabetic (NOD) mouse model of type 1 diabetes. PPARs are thus of interest in type 1 diabetes (T1D) as they represent a novel approach targeting both the pancreas and the immune system. In this review, we examine the role of PPARs in immune responses and beta cell biology and their potential as targets for treatment of T1D.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2020 ","pages":"6198628"},"PeriodicalIF":2.9,"publicationDate":"2020-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/6198628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37923567","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":"Piperine Alleviates Doxorubicin-Induced Cardiotoxicity via Activating PPAR-<i>γ</i> in Mice.","authors":"Jie Yan,&nbsp;Si-Chi Xu,&nbsp;Chun-Yan Kong,&nbsp;Xiao-Yang Zhou,&nbsp;Zhou-Yan Bian,&nbsp;Ling Yan,&nbsp;Qi-Zhu Tang","doi":"10.1155/2019/2601408","DOIUrl":"https://doi.org/10.1155/2019/2601408","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress, inflammation and cardiac apoptosis were closely involved in doxorubicin (DOX)-induced cardiac injury. Piperine has been reported to suppress inflammatory response and pyroptosis in macrophages. However, whether piperine could protect the mice against DOX-related cardiac injury remain unclear. This study aimed to investigate whether piperine inhibited DOX-related cardiac injury in mice.</p><p><strong>Methods: </strong>To induce DOX-related acute cardiac injury, mice in DOX group were intraperitoneally injected with a single dose of DOX (15 mg/kg). To investigate the protective effects of piperine, mice were orally treated for 3 weeks with piperine (50 mg/kg, 18:00 every day) beginning two weeks before DOX injection.</p><p><strong>Results: </strong>Piperine treatment significantly alleviated DOX-induced cardiac injury, and improved cardiac function. Piperine also reduced myocardial oxidative stress, inflammation and apoptosis in mice with DOX injection. Piperine also improved cell viability, and reduced oxidative damage and inflammatory factors in cardiomyocytes. We also found that piperine activated peroxisome proliferator-activated receptor-<i>γ</i> (PPAR-<i>γ</i>), and the protective effects of piperine were abolished by the treatment of the PPAR-<i>γ</i> antagonist in vivo and in vitro.</p><p><strong>Conclusions: </strong>Piperine could suppress DOX-related cardiac injury via activation of PPAR-<i>γ</i> in mice.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2019 ","pages":"2601408"},"PeriodicalIF":2.9,"publicationDate":"2019-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/2601408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37539008","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 Ligand Inhibits Nasopharyngeal Carcinoma Cell Proliferation and Metastasis by Regulating E2F2","authors":"Ping Yang, Jiashui Wang, Xiaoxia Cheng, Jingchao Chen, Hui Zhu, Xiaolin Li, Li Cao, Wei-Wei Tang","doi":"10.1155/2019/8679271","DOIUrl":"https://doi.org/10.1155/2019/8679271","url":null,"abstract":"Purpose Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear hormone receptor with a key role in lipid metabolism. Previous studies have identified various roles of PPAR-γ in cell cycle progression, cellular proliferation, and tumor progression. However, no report has described a role for PPAR-γ in human nasopharyngeal carcinoma (NPC). Notably, some studies have reported a relationship between PPAR-γ and E2F transcription factor 2 (E2F2), which has been identified as a regulator of cell cycle, apoptosis, and the DNA damage response. Notably, E2F2 has also been reported to correlate with a poor prognosis in patients with various malignancies. Methods We used immunohistochemical (IHC) and western blot methods to evaluate PPAR-γ and E2F2 expression and function in nonkeratinizing NPC and nasopharyngitis (NPG) tissue samples, as well as western blotting and CCK8 analyses in the NPC cell lines, CNE1 and CNE2. Results We observed lower levels of PPAR-γ expression in nonkeratinizing NPC tissues compared with NPG tissues and determined an association between a low level of PPAR-γ expression with a more advanced tumor stage. Furthermore, strong E2F2 expression was detected in nonkeratinizing NPC tissues. We further demonstrated that rosiglitazone, a PPAR-γ agonist, reduced E2F2 expression and proliferation in NPC cell lines. Conclusions Our study results revealed a novel role for the PPAR-γ–E2F2 pathway in controlling NPC cell proliferation and metastasis.","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/8679271","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43105056","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":"15-Deoxy-∆-12,14-Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-γ: Function and Mechanism","authors":"Jingjing Li, Chuanyong Guo, Jianye Wu","doi":"10.1155/2019/7242030","DOIUrl":"https://doi.org/10.1155/2019/7242030","url":null,"abstract":"15-Deoxy-∆-12,14-prostaglandin J2 (15d-PGJ2), a natural peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has been explored in some detail over the last 20 years. By triggering the PPAR-γ signalling pathway, it plays many roles and exerts antitumour, anti-inflammatory, antioxidation, antifibrosis, and antiangiogenesis effects. Although many synthetic PPAR-γ receptor agonists have been developed, as an endogenous product of PPAR-γ receptors, 15d-PGJ2 has beneficial characteristics including rapid expression and the ability to contribute to a natural defence mechanism. In this review, we discuss the latest advances in our knowledge of the biological role of 15d-PGJ2 mediated through PPAR-γ. It is important to understand its structure, synthesis, and functional mechanisms to develop preventive agents and limit the progression of associated diseases.","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/7242030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46585936","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":"Corrigendum to “PPARs in Human Neuroepithelial Tumors: PPAR Ligands as Anticancer Therapies for the Most Common Human Neuroepithelial Tumors”","authors":"E. Benedetti, R. Galzio, B. D'angelo, M. Ceru', A. Cimini","doi":"10.1155/2019/4309068","DOIUrl":"https://doi.org/10.1155/2019/4309068","url":null,"abstract":"[This corrects the article DOI: 10.1155/2010/427401.].","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/4309068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49033670","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":"Retracted: Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats","authors":"PPAR Research","doi":"10.1155/2019/9760941","DOIUrl":"https://doi.org/10.1155/2019/9760941","url":null,"abstract":"[This retracts the article DOI: 10.1155/2016/9282087.].","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/9760941","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42403823","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":"Activation and Expression of Peroxisome Proliferator-Activated Receptor Alpha Are Associated with Tumorigenesis in Colorectal Carcinoma","authors":"Tatsuya Morinishi, Yasunori Tokuhara, H. Ohsaki, Emi Ibuki, K. Kadota, E. Hirakawa","doi":"10.1155/2019/7486727","DOIUrl":"https://doi.org/10.1155/2019/7486727","url":null,"abstract":"Peroxisome proliferator-activated receptor alpha (PPAR-α) belongs to the PPAR family and plays a critical role in inhibiting cell proliferation and tumorigenesis in various tumors. However, the role of PPAR-α in colorectal tumorigenesis is unclear. In the present study, we found that fenofibrate, a PPAR-α agonist, significantly inhibited cell proliferation and induced apoptosis in colorectal carcinoma cells. In addition, PPAR-α was expressed in the nucleus of colorectal carcinoma cells, and the expression of nuclear PPAR-α increased in colorectal carcinoma tissue compared with that of normal epithelium tissue (P<0.01). The correlation between the expression of nuclear PPAR-α and clinicopathological factors was evaluated in human colorectal carcinoma tissues, and the nuclear expression of PPAR-α was significantly higher in well-to-moderately differentiated adenocarcinoma than in mucinous adenocarcinoma (P<0.05). These findings indicate that activation of PPAR-α may be involved in anticancer effects in colorectal carcinomas, and nuclear expression of PPAR-α may be a therapeutic target for colorectal adenocarcinoma treatment.","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/7486727","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44527608","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 Antagonizes LOX-1-Mediated Endothelial Injury by Transcriptional Activation of miR-590-5p","authors":"Lei Xu, Gang Zhao, Hong Zhu, Shijun Wang, A. Sun, Y. Zou, J. Ge","doi":"10.1155/2019/2715176","DOIUrl":"https://doi.org/10.1155/2019/2715176","url":null,"abstract":"Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is one of the major receptors expressed on the endothelium of arterial wall with a key role in endothelial dysfunction and the development of atherosclerosis. Recent evidence suggested that LOX-1 is upregulated under the condition of insulin resistance and could be suppressed by the antidiabetic drugs. We previously also confirmed that Thiazolidinedione (TZD) has the inhibitory effect on LOX-1 in ox-LDL-induced endothelial cells. However, the underlying mechanism is unclear. Here we showed that Rosiglitazone treatment significantly attenuated the expressions of LOX-1, ICAM-1, VCAM-1, p47phox, and the atherosclerotic lesions in ApoE−/− mice with high-fat diet. In vitro, we revealed that Rosiglitazone inhibited LOX-1 by regulating miR-590-5p. Ox-LDL-mediated ICAM-1, VCAM-1, and p47phox were significantly reduced by Rosiglitazone, but all reversed after pretreating the cells with antagomiR-590-5p. Induction with Rosiglitazone activated PPAR-γ and promoted its nuclear translocation in cultured human umbilical vein endothelial cells (HUVECs). The nuclear PPAR-γ upregulated the miR-590-5p level through binding to its transcriptional promoter region. Retaining PPAR-γ in cytoplasm by transfecting with PPAR-γ⊿NLS plasmid in HUVECs failed to activate miR-590-5p. Mutation of the promoter region of PPAR-γ also reduced the miR-590-5p promoter luciferase activity. Collectively, these data indicated that PPAR-γ may have the therapeutic potential in atherosclerosis via the transcriptional regulation of miR-590-5p in endothelial cells.","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/2715176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44875453","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}