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peroxisome proliferator-activated receptors as targets to treat metabolic diseases:Focus on the adipose tissue,liver,and pancreas

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World Journal of Gastroenterology 2023年第26期29卷 4136-4155页

作者： Henrique Souza-Tavares Carolline Santos Miranda Isabela Macedo Lopes Vasques-Monteiro Cristian Sandoval Daiana Araujo Santana-Oliveira Flavia Maria Silva-Veiga Aline Fernandes-da-Silva Vanessa Souza-Mello Department of Anatomy Rio de Janeiro State UniversityRio de Janeiro 20551030Brazil Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásOsorno 5310431Chile Departamento de Ciencias Preclínicas Universidad de la FronteraTemuco 4780000Chile

The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease *** prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its *** adipose tissue is the initial site of obesity *** excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other *** pancreas is one of the organs most affected by *** lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long *** for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic *** silent disease affects around 30%of the worldwide population and can evolve into end-stage liver *** therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM *** PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial *** review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.

关键词： Obesity Insulin resistance peroxisome proliferator-activated receptors Pancreas Hepatic steatosis Adipose tissue

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peroxisome proliferator-activated receptors for hypertension

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World Journal of Cardiology 2014年第8期6卷 744-754页

作者： Daisuke Usuda Tsugiyasu Kanda Department of Community Medicine Kanazawa Medical University Himi Municipal HospitalHimi-shi 935-8531Toyama-kenJapan

peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be *** article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases.

关键词： peroxisome proliferator-activated receptors Nuclear receptor Isoform mRNA Blood pressure Hypertension Obesity Angiotensin II receptor blocker Diabetes mellitus

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An innovative approach for the treatment of Alzheimer's disease: the role of peroxisome proliferator-activated receptors and their ligands in development of alternative therapeutic interventions

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Neural Regeneration Research 2019年第1期14卷 43-45页

作者： Luca Piemontese Dipartimento Farmacia-Scienze del Farmaco Università degli Studi di Bari "Aldo Moro"

Alzheimer＇s disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment, q-his innovative approach will lead to the identification of new targets for the preparation of new effective drugs. peroxisome proliferator-activated receptors and their ligands are the ideal candidates to reach the necessary breakthrough to defeat this complicate disease.

关键词： Alzheimer's disease multifunctional drugs peroxisome proliferator-activated receptors type 3 diabetes innovative therapies type 2 diabetes mellitus metabolism neuroinflammation

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Inflammatory reaction versus endogenous peroxisome proliferator- activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats

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Chinese Medical Journal 2008年第22期121卷 2305-2311页

作者： SUN Li KE Yan ZHU Chun-yun TANG Ning TIAN Deng-ke GAO Yue-hong ZHENG Jian-pu BIAN Ka Murad Research Institute for Modernized Chinese Medicine Shanghai University of Traditional Chinese Medicine Shanghai 201203 China Tianjin Medical University General Hospital Tianjin 300052 China Division of Nitric Oxide and Inflammatory Medicine E-Institute of Shanghai Universities Shanghai 201203 China Department of Integrative Biology and Pharmacology Institute of Molecular Medicine University of Texas Medical School 6431 Fannin Houston TX 77030 USA

Background The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors （PPARs） have been identified： PPARa, PPARβ/δ, and PPARγ, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats （SHR） and to understand the modulation of endogenous PPAR isoforms under inflammatory condition. Methods l]ssues （kidney, liver, heart, and brain） were dissected from SHR and age-matched control Wistar-Kyoto rats （WKY） to investigate the abundance of PPAR isoforms and PPAR-responsive genes （acyI-CoA oxidase and CD36）. The expression of CCAAT/enhancer-binding protein 6 （C/EBP6）, which can trans-activate PPARγ expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase （iNOS）, intercellular adhesion molecule-1 （ICAM-1）, vascular cell adhesion molecule-1 （VCAM-1）, E-selectin, interleukin-1 beta （IL-1β）, and tumor necrosis factor alpha （TNFα）, and formation of carbonyl and nitrated proteins. Results The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPARβ/δ upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARγ increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARy, the expression of C/EBPδ was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbony

关键词： spontaneously hypertensive rats inflammation peroxisome proliferator-activated receptors

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peroxisome proliferator-activated receptor agonists:A new hope towards the management of alcoholic liver disease

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World Journal of Gastroenterology 2024年第35期30卷 3965-3971页

作者： Siva Sundara Kumar Durairajan Abhay Kumar Singh Ashok Iyaswamy Department of Microbiology School of Life SciencesCentral University of Tamil NaduTiruvarur 610005India School of Biomedical Sciences Li Ka Shing Faculty of MedicineUniversity of Hong KongHong Kong 999077China School of Chinese Medicine Hong Kong Baptist UniversityHong Kong 999077China Department of Biochemistry Karpagam Academy of Higher EducationCoimbatore 641021India

In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of *** study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by *** therapies are necessary for ALD because it is a critical health issue that affects people *** editorial analyzes the possibility of PPAR agonists as treatments for *** key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of *** assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver *** research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver *** editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for *** research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.

关键词： Alcoholic liver disease peroxisome proliferator-activated receptors peroxisome proliferator-activated receptors agonists Liver fibrosis Inflammation Metabolic regulation Hepatoprotection

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EFFECT OF peroxisome proliferator-activated RECEPTOR ACTIVATORS ON TUMOR NECROSIS FACTOR-αEXPRESSION IN NEONATAL RAT CARDIAC MYOCYTES

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Chinese Medical Sciences Journal 2004年第4期19卷 243-247页

作者： PingYe HongFang XinZhou Yan-liHe Yong-xueLiu CenterofGeneticDiagnosis SouthcenterHospitalWuhanUniversityWuhan430071 InstituteofRadiationMedicine AcademyofMilitaryMedicalScienceBeijing100850 DepartmentofGeriatricCardiology ChinesePeople＇sLiberationArmyGeneralHospitalBeijing100853

Objective To investigate the effect of peroxisome proliferator-activated receptor-α(PPARα) and PPARγactivators on tumor necrosis factor-α(TNFα) expression in neonatal rat cardiac myocytes. Methods Primary cultures of cardiac myocytes from 1- to 3-day-old Wistar rats were prepared, and myocytes were ex-posed to lipopolysaccharide (LPS) and varying concentrations of PPARαor PPARγactivator (fenofibrate or pioglitazone).RT-PCR and ELISA were used to measure TNFα, PPARα, and PPARγexpression in cultured cardiac myocytes. Transient tr-ansfection of TNFαpromoter with or without nuclear factor-kappaB (NF-κB) binding site to cardiac myocytes was performed. Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFαmRNA and protein expression in a dose-dependent manner. However, no significant changes were observed on PPARαor PPARγmRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone. Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFαpromoter (-721/+17) after being stimulated with LPS and fenofibrate or pioglitazone, whereas no change of promoter activity was observed with transfection of TNFαreporter construct in deletion of NF-κB binding site (-182/+17). Conclusions PPARαand PPARγactivators may inhibit cardiac TNFαexpression but not accompanied by change of PPARαor PPARγmRNA expression. Therefore PPARαand PPARγactivators appear to play a role in anti-inflammation. The mechanism may partly be involved in suppression of the NF-κB pathway.

关键词： peroxisome proliferator-activated receptors tumor necrosis factor-α cardiac myocytes activators

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Activation of peroxisome proliferator-activated receptor α in human endothelial cells increases plasminogen activator inhibitor type-1 expression

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Chinese Medical Journal 2003年第1期116卷 29-33页

作者：叶平胡晓晖刘永学赵亚力 Department of Geriatric Cardiology Academy of Military Medical Sciences

Objective To investigate the effect of peroxisome proliferator-activated receptors (PPARs) activators on plasminogen activator inhibitor 1 (PAI-1) expression in human umbilical vein endothelial cells and elucidate a possible mechanism. Methods Human umbilical vein endothelial cells (HUVECs) were obtained from normal fetus, and cultured conventionally. Then the HUVEC were exposed to fatty acids and prostaglandin J 2 in varying concentrations with fresh media. RT-PCR and ELISA were used to determine the expression of PPAR and PAI-1 in HUVECs. Transient co-transfection of PAI-1 promoter and PPARα gene or PPARγ gene to ECV304 was *** PPARα, PPARδ and PPARγ mRNA in HUVECs were detected by RT-PCR. Treatment of HUVECs with PPARα and PPARγ activators-linolenic acid, linoleic acid, oleic acid and prostaglandin J 2, but not with stearic acid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner. Proportional induction of PAI-1 promoter activity was observed through increasing amounts of PPARα DNA in HUVECs through a transient gene transfection assay, although the mRNA expression of the 3 subtypes of PPAR with their activators were not changed compared with *** HUVECs express PPARs. PPARs activators may increase PAI-1 expression in endothelial cells (EC). Although PPARs expression was not enhanced after being stimulated by their activators in EC, the functionally active PPARα is probably involved in regulating PAI-1 expression in EC.

关键词： peroxisome proliferator-activated receptors plasminogen activator inhibitor 1 umbilical veins

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Bailing capsule(百令胶囊)alleviates autoimmune thyroiditis via regulating peroxisome proliferator-activated receptor signaling pathway:a multi-omics analysis

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Journal of Traditional Chinese Medicine 2024年第6期44卷 1217-1226页

作者： WANG Qixin XU Liting WU Jiangpeng HE Xueling TANG Huan CHENG Guangqing LU Tianming DAI Chuanhao GUO Qiuyan WANG Jigang State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences School of Chinese Materia Medica and State Key Laboratory of Component-based Chinese MedicineTianjin University of Traditional Chinese Medicine

OBJECTIVE: To investigate the efficacy and potential mechanism of Bailing capsule( 百令胶囊, BL) antiautoimmune thyroiditis(AIT). METHODS: Based on the AIT rat model, the effect of BL in alleviating AIT was evaluated by detecting serum thyroid index free triiodothyronine(FT3), free thyroxine(FT4), thyroid-stimulating hormone(TSH), thyroglobulin antibody(TGAb), thyroid peroxidase antibody(TPOAb), and inflammatory factors Interferon-gamma(IFN-γ), Interleukin-4,-10, and-12(IL-4, IL-10, and IL-12) as well as thyroid tissue Hematoxylin-eosin(HE) staining and ultrastructure observation. The mechanism of BL was explored by combining transcriptome and proteome analysis, and further verified by Western blot(WB). RESULTS: BL effectively reduced serum FT3, FT4, TGAb, and TPOAb levels in AIT rats, restored TSH balance, inhibited the release of pro-inflammatory cytokines IFN-γ and IL-12, promoted the production of anti-inflammatory cytokines IL-4 and IL-10, and significantly reduced IFN-γ/IL-4 and IL-12/IL-10, improved thyroid follicular structure, and protected thyroid tissue from injury. Kyoto Encyclopedia of Genes and Genomes and protein interaction network analysis showed that BL affected the expression of fatty acidbinding protein 4, acyl-Co A synthetase long-chain family member 1, and acyl-Co A dehydrogenase long chain to regulate the peroxisome proliferator-activated receptor signaling pathway, thereby inhibiting the fatty acid metabolism and the inflammatory state of AIT ***: BL could effectively reduce thyroid inflammation in AIT model rats. The possible BL mechanism was to regulate the peroxisome proliferatoractivated receptor signaling pathway and inhibit fatty acid metabolism. This study suggested that BL has the potential to be used in clinical treatment of AIT.

关键词： Bailing capsule cordyceps fatty acid peroxisome proliferator-activated receptors thyroiditis, autoimmune

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Data-driven analysis of chemicals,proteins and pathways associated with peanut allergy:from molecular networking to biological interpretation

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Food Science and Human Wellness 2024年第3期13卷 1322-1335页

作者： Emmanuel Kemmler Julian Braun Florent Fauchère Sabine Dölle-Bierke Kirsten Beyer Robert Preissner Margitta Worm Priyanka Banerjee Institute for Physiology Charité-University Medicine BerlinBerlin 10115Germany Member of the KFO339 FOOD@Berlin 10115Germany Si-M/“Der Simulierte Mensch”a science framework of Technische Universität Berlin and Charité-Universitätsmedizin Berlin Berlin 10115Germany Charité-Universitätsmedizin Berlin corporate member of Freie Universität BerlinHumboldt-Universität zu Berlinand Berlin Institute of HealthBerlin 10115Germany Division of Allergy and Immunology Department of DermatologyVenerology and AllergyCharité-Universitätsmedizin Berlincorporate member of Freie Universität Berlin and Humboldt-Universität zu BerlinBerlin 10115Germany Pediatrics Campus VirchowCharité-University Medicine BerlinBerlin 10115Germany

Peanut allergy is majorly related to severe food induced allergic *** food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food ***,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and ***,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and *** the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic *** results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.

关键词： Allergy informatics Knowledge-graph Data analysis Food allergy peroxisome proliferator-activated receptors Fatty acids

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Design,synthesis and in vitro evaluation of a series thiazolidinediones analogs as PPAR modulators

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Chinese Chemical Letters 2007年第1期18卷 45-47页

作者： Jun Feng Ying Lu Zhe Feng Cai Shi Peng Zhang Zong Ru Guo Institute of Materia Medica Chinese Academy of Medical Science and Peking Union Medical College Beijing 100050 China

A series of thiazolidinediones analogs, as PPAR modulators, were designed, synthesized and evaluated in vitro.

关键词： peroxisome proliferator-activated receptors PPAR modulators Thiazolidinediones

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