DOCSLIB.ORG

The Role of PPAR and Its Cross-Talk with CAR and LXR in Obesity and Atherosclerosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of PPAR and Its Cross-Talk with CAR and LXR in Obesity and Atherosclerosis International Journal of Molecular Sciences Review The Role of PPAR and Its Cross-Talk with CAR and LXR in Obesity and Atherosclerosis Pengfei Xu 1,2, Yonggong Zhai 1,2,* and Jing Wang 3,* 1 Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China; [email protected] 2 Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China 3 Department of Biology Science and Technology, Baotou Teacher’s College, Baotou 014030, China * Correspondence: [email protected] (Y.Z.); [email protected] (J.W.); Tel.: +86-10-5880-6656 (Y.Z.); +86-186-482-6849 (J.W.) Received: 26 March 2018; Accepted: 19 April 2018; Published: 23 April 2018 Abstract: The prevalence of obesity and atherosclerosis has substantially increased worldwide over the past several decades. Peroxisome proliferator-activated receptors (PPARs), as fatty acids sensors, have been therapeutic targets in several human lipid metabolic diseases, such as obesity, atherosclerosis, diabetes, hyperlipidaemia, and non-alcoholic fatty liver disease. Constitutive androstane receptor (CAR) and liver X receptors (LXRs) were also reported as potential therapeutic targets for the treatment of obesity and atherosclerosis, respectively. Further clarification of the internal relationships between these three lipid metabolic nuclear receptors is necessary to enable drug discovery. In this review, we mainly summarized the cross-talk of PPARs-CAR in obesity and PPARs-LXRs in atherosclerosis. Keywords: PPAR; CAR; LXR; obesity; atherosclerosis 1. Introduction Obesity is a lipid metabolic disturbance that has been growing across the world for nearly half a century. It is a global human health concern. In 2016, more than 1.9 billion adults (≥18 years old) were overweight and, of these, over 650 million were obese. Furthermore, 340 million children and adolescents (5–18 years old) and 41 million children (≤5 years old) were overweight or obese [1,2]. The body mass index (BMI), defined as a person’s weight in kilograms divided by the square of their height in meters, is a simple index used to classify overweight and obesity in adults. Obesity is associated with various metabolic disorders and cardiovascular diseases. A high BMI is considered to be an indicator of high body fatness that may lead to a high risk of cardiometabolic syndrome and atherosclerotic vascular disease [3–5]. Atherosclerosis, also known as arteriosclerosis, hardening of the arteries, is a disease in which fatty plaque deposits build up inside the arteries, narrowing them, leading to some serious problems, including coronary artery disease, stroke, or even death [6]. Obesity and atherosclerosis are common chronic lipid metabolic disorder diseases. The treatment and prevention of obesity and atherosclerosis are both major challenges, and studying this problem can help us live longer, healthier lives. Nuclear receptors (NRs), a class of ligand-activated transcriptional factors, play significant roles in metabolic homeostasis. It is well known that there are 48 and 49 NR genes in humans (Homo sapiens) and mice (Mus musculus), respectively [7,8]. Most of the NRs contain six functional domains, such as the variable N-terminal regulatory domain (A–B), the conserved DNA-binding domain (DBD) (C), the variable hinge region (D), the conserved ligand binding domain (LBD) (E), and the variable Int. J. Mol. Sci. 2018, 19, 1260; doi:10.3390/ijms19041260 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2018, 19, 1260 2 of 17 C-terminalInt. J. Mol. Sci. domain 2018, 19, (F)x FOR (Figure PEER REVIEW1a) [ 7, 9 ]. The classical function of NRs is to transcriptionally regulate2 of 17 the expression of cognate target genes through the recruitment of coactivators or corepressors when ligandsexpression bind of to thecognate receptors target [10genes,11] (Figurethrough1 b).the Torecruitment perform theof coactivators transcriptional or corepressors activity, NRs when either ligands bind to the receptors [10,11] (Figure 1b). To perform the transcriptional activity, NRs either (1) act as monomers; (2) need to form dimeric complexes (homodimers); or (3) form complexes with (1) act as monomers; (2) need to form dimeric complexes (homodimers); or (3) form complexes with the retinoid X receptor (RXR) (heterodimers) and bind to the DNA in the cell nucleus [9]. Recently, the retinoid X receptor (RXR) (heterodimers) and bind to the DNA in the cell nucleus [9]. Recently, many studies have indicated the role of some NRs in the regulation of lipid metabolism. It has many studies have indicated the role of some NRs in the regulation of lipid metabolism. It has been been recognized that peroxisome proliferator-activated receptors (PPARs) act as fatty acid sensors, recognized that peroxisome proliferator-activated receptors (PPARs) act as fatty acid sensors, regulatingregulating the the multiple multiple pathwayspathways involvedinvolved in lipid lipid and and glucose glucose metabolism metabolism and and overall overall energy energy metabolismmetabolism [12 [12,13,13].]. Furthermore,Furthermore, thethe constitutive androstane androstane receptor receptor (CAR), (CAR), which which was was initially initially characterizedcharacterized as as a a xenosensor xenosensor thatthat controlscontrols xenobiotic responses, responses, has has been been recently recently identified identified as asa a therapeutictherapeutic target target for for obesity obesity andand itsits relatedrelated metabolic disorders disorders [14,15 [14,15], ],whereas whereas liver liver X Xreceptors receptors (LXRs)(LXRs) are are sterol sterol sensors sensors that that mainly mainly regulate regulate cholesterol, cholesterol, fatty fatty acid acid and and glucose glucose homeostasis, homeostasis, they they can inhibitcan inhibit atherosclerosis atherosclerosis development, development, but promote but promote lipogenesis lipogenesis in liver in liver [16]. [16]. In this In review,this review, we brieflywe summarizebriefly summarize the roles the of PPARs, roles of CARPPARs, and CAR LXRs and and LXRs their and ligands their ligands in the treatment in the treatment of metabolic of metabolic diseases, obesitydiseases, and obesity atherosclerosis, and atherosclerosis and discuss, and di thescuss cross-talk the cross of-talk PPARs-CAR of PPARs-CAR and and PPARs-LXRs PPARs-LXRs in lipidin metabolismlipid metabolism regulation. regulation. FigureFigure 1. 1.Schematic Schematic structure structure ofof NRsNRs (nuclear(nuclear receptors) and and model model of of NR NR signalling signalling.. (a) ( aGeneral) General domaindomain structure structure of of NRs; NRs; and and (b(b)) thethe mechanismmechanism of general general NR NR action. action. The The ligands ligands bind bind to tothe the LBD LBD (ligand-binding(ligand-binding domain) domain) ofof NRsNRs inin thethe cytoplasm,cytoplasm, and translocate translocate to to the the nucleus. nucleus. Then Then the the DBD DBD (DNA-binding(DNA-binding domain) domain) ofof NRsNRs bindbind toto thethe XRE (xenobiotic responsive responsive elements) elements) form forminging dimeric dimeric complexescomplexes with with RXR RXR and and the the recruitmentrecruitment of co-activatorsco-activators or or co co-repressors.-repressors. Finally, Finally, this this leads leads to tothe the transcriptiontranscription of of the the target target genes. genes. ThisThis model is is applied applied to to type type II II NRs, NRs, including including PPARs, PPARs, CAR, CAR, LXRs LXRs,, andand others. others. The The colorful colorful words words justjust matchmatch the corresponding colorful colorful shape. shape. The The dotted dotted arrows arrows mean mean differentdifferent ligands ligands can can recruit recruit coactivators coactivators oror corepressorscorepressors to form form dimers, dimers, respectively. respectively. 2. The Initial Characterization of PPAR, CAR, and LXR 2. The Initial Characterization of PPAR, CAR, and LXR 2.1.2.1. Fatty Fatty Acids Acids Sensor Sensor PPARs PPARs PPARs are molecular sensors of fatty acids and fatty acid derivatives and control energy PPARs are molecular sensors of fatty acids and fatty acid derivatives and control energy homeostasis (carbohydrate, lipid, and protein) [17]. There are three types of PPARs which have been homeostasis (carbohydrate, lipid, and protein) [17]. There are three types of PPARs which have identified: PPARα (NR1C1, encoded by PPARA), PPARβ/δ (NR1C2, encoded by PPARD), and Int. J. Mol. Sci. 2018, 19, 1260 3 of 17 been identified: PPARα (NR1C1, encoded by PPARA), PPARβ/δ (NR1C2, encoded by PPARD), and PPARγ (NR1C3, encoded by PPARG). They are all lipid sensors that transcriptionally regulate diverse aspects in response to nutritional inputs, and serving as effective therapeutic targets for some types of lipid metabolic syndrome, including obesity, atherosclerosis, dyslipidaemia, type 2 diabetes mellitus (T2DM), and nonalcoholic fatty liver disease (NAFLD) [12,18]. PPARα is highly active in liver, brown adipose tissue (BAT), kidney, heart, and muscle tissue [19], where it regulates the adaptive response to prolonged fasting by controlling the process of ketogenesis, fatty acid transport, fatty acid binding, fatty acid activation and mitochondrial fatty acid β-oxidation [20,21]. Genomic studies have indicated that PPARα, as a master regulator of lipid metabolism, has various target genes; the classical genes include acyl-CoA oxidase, thiolase, fatty
Load more

Recommended publications
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Diabetes-Related Biomarkers and Methods of Use Thereof
    (19) TZZ _ _T (11) EP 2 541 254 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: G01N 21/76 (2006.01) G01N 21/64 (2006.01) 12.11.2014 Bulletin 2014/46 G01N 33/66 (2006.01) G01N 33/74 (2006.01) G01N 33/68 (2006.01) (21) Application number: 12175286.9 (22) Date of filing: 18.04.2008 (54) Diabetes-related biomarkers and methods of use thereof Diabetesassoziierte Biomarker und Verfahren zur deren Verwendung dafür Biomarqueurs associés aux diabètes et procédés d’utilisation correspondants (84) Designated Contracting States: • HANLEY ANTHONY J G ET AL: "Metabolic and AT BE BG CH CY CZ DE DK EE ES FI FR GB GR inflammation variable clusters and prediction of HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT type 2 diabetes: factor analysis using directly RO SE SI SK TR measured insulin sensitivity.", DIABETES JUL 2004, vol. 53, no. 7, July 2004 (2004-07), pages (30) Priority: 18.04.2007 US 788260 1773-1781, XP002486180, ISSN: 0012-1797 08.11.2007 US 2609 P • EDELMAN DAVID ET AL: "Utility of hemoglobin A1c in predicting diabetes risk", JOURNAL OF (43) Date of publication of application: GENERAL INTERNAL MEDICINE, vol. 19, no. 12, 02.01.2013 Bulletin 2013/01 December 2004 (2004-12), pages 1175-1180, XP002502995, ISSN: 0884-8734 (62) Document number(s) of the earlier application(s) in • INOUE ET AL: "The combination of fasting accordance with Art. 76 EPC: plasma glucose and glycosylated hemoglobin 08746276.8 / 2 147 315 predicts type 2 diabetes in Japanese workers", DIABETES RESEARCH AND CLINICAL (73) Proprietor: Health Diagnostic Laboratory, Inc.
    [Show full text]
  • The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development
    International Journal of Molecular Sciences Review The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development Fan Hong 1,2, Pengfei Xu 1,*,† and Yonggong Zhai 1,2,* 1 Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China; [email protected] 2 Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China * Correspondence: [email protected] (P.X.); [email protected] (Y.Z.); Tel.: +86-156-005-60991 (P.X.); +86-10-5880-6656 (Y.Z.) † Current address: Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA. Received: 22 June 2018; Accepted: 24 July 2018; Published: 27 July 2018 Abstract: Peroxisome proliferator-activated receptors (PPARs) are a well-known pharmacological target for the treatment of multiple diseases, including diabetes mellitus, dyslipidemia, cardiovascular diseases and even primary biliary cholangitis, gout, cancer, Alzheimer’s disease and ulcerative colitis. The three PPAR isoforms (α, β/δ and γ) have emerged as integrators of glucose and lipid metabolic signaling networks. Typically, PPARα is activated by fibrates, which are commonly used therapeutic agents in the treatment of dyslipidemia. The pharmacological activators of PPARγ include thiazolidinediones (TZDs), which are insulin sensitizers used in the treatment of type 2 diabetes mellitus (T2DM), despite some drawbacks. In this review, we summarize 84 types of PPAR synthetic ligands introduced to date for the treatment of metabolic and other diseases and provide a comprehensive analysis of the current applications and problems of these ligands in clinical drug discovery and development.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Regulation of Pharmaceutical Prices: Evidence from a Reference Price Reform in Denmark
    A Service of Leibniz-Informationszentrum econstor Wirtschaft Leibniz Information Centre Make Your Publications Visible. zbw for Economics Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas Working Paper Regulation of pharmaceutical prices: Evidence from a reference price reform in Denmark ZEW Discussion Papers, No. 10-062 Provided in Cooperation with: ZEW - Leibniz Centre for European Economic Research Suggested Citation: Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas (2010) : Regulation of pharmaceutical prices: Evidence from a reference price reform in Denmark, ZEW Discussion Papers, No. 10-062, Zentrum für Europäische Wirtschaftsforschung (ZEW), Mannheim This Version is available at: http://hdl.handle.net/10419/41440 Standard-Nutzungsbedingungen: Terms of use: Die Dokumente auf EconStor dürfen zu eigenen wissenschaftlichen Documents in EconStor may be saved and copied for your Zwecken und zum Privatgebrauch gespeichert und kopiert werden. personal and scholarly purposes. Sie dürfen die Dokumente nicht für öffentliche oder kommerzielle You are not to copy documents for public or commercial Zwecke vervielfältigen, öffentlich ausstellen, öffentlich zugänglich purposes, to exhibit the documents publicly, to make them machen, vertreiben oder anderweitig nutzen. publicly available on the internet, or to distribute or otherwise use the documents in public. Sofern die Verfasser die Dokumente unter Open-Content-Lizenzen (insbesondere CC-Lizenzen) zur Verfügung gestellt haben sollten, If the documents have been made available under an Open gelten abweichend von diesen Nutzungsbedingungen die in der dort Content Licence (especially Creative Commons Licences), you genannten Lizenz gewährten Nutzungsrechte. may exercise further usage rights as specified in the indicated licence. www.econstor.eu Dis cus si on Paper No. 10-062 Regulation of Pharmaceutical Prices: Evidence from a Reference Price Reform in Denmark Ulrich Kaiser, Susan J.
    [Show full text]
  • 2013 Proceedings Annual Conference AAZV 1 GEORGIA WILDLIFE HEALTH PROGRAM and the GEORGIA SEA TURTLE CENTER Terry M. Norton
    GEORGIA WILDLIFE HEALTH PROGRAM AND THE GEORGIA SEA TURTLE CENTER Terry M. Norton, DVM, Dipl ACZM Georgia Sea Turtle Center, Jekyll Island Authority, Jekyll Island, GA 31527 USA Abstract Throughout my veterinary career I have been very interested in free-ranging wildlife. While working on St. Catherines Island (SCI) in coastal Georgia, I was able to develop the Georgia Wildlife Health Program. The primary goals of this program are to assist conservation organizations on various aspects of wildlife health and disease issues and to provide veterinary services to wildlife biologists and graduate students. The focus of the program has been on health related issues pertaining to wild reptiles and birds.1-3, 6-10, 12-16 In 2000, we partnered with the Wildlife Conservation Society’s (WCS) Field Veterinary Program on a global sea turtle health assessment project.4 Georgia was added as the North American site because of the relationship WCS had with SCI. The work in Georgia included establishing baseline health parameters for several of the life stages of the loggerhead sea turtle.5 In addition to evaluating healthy turtles, we started to be called upon to do the initial evaluation of stranded sea turtles. Through this work, it became apparent that a sea turtle rehabilitation center was needed in coastal Georgia.11 The original site for the facility was to be on SCI, a remote barrier island which is only assessable by boat. I started to fund raise on my own by writing grants and developing some unique methods to raise awareness and funding. The “Turtle Crawl” was established in 2003 with the goal of creating awareness and raising funds for the Georgia Sea Turtle Center (GSTC).
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • 2 12/ 35 74Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 22 March 2012 (22.03.2012) 2 12/ 35 74 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/16 (2006.01) A61K 9/51 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 9/14 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/065959 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 14 September 201 1 (14.09.201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/382,653 14 September 2010 (14.09.2010) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, NANOLOGICA AB [SE/SE]; P.O Box 8182, S-104 20 ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Stockholm (SE).
    [Show full text]
  • Peroxisome Proliferator-Activated Receptors As Superior Targets to Treat Diabetic Disease, Design Strategies - Review Article
    Review article DOI: 10.4274/tjps.galenos.2021.70105 Peroxisome proliferator-activated receptors as superior targets to treat diabetic disease, design strategies - review article Diyabetik hastalığı tedavi etmek için üstün hedefler olarak peroksizom proliferatör ile aktive edilmiş reseptörler, tasarım stratejileri - inceleme makalesi Mohammed T Qaoud1, Ihab Al-masri2, Tijen Önkol1 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara- Turkey 2Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Al Azhar University, Gaza Strip, Palestine proof Corresponding Author Mohammed T Qaoud, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gazi University, Ankara-Turkey [email protected] +90 552 634 15 56 https://orcid.org/0000-0002-9563-9493 09.12.2020 31.05.2021 09.06.2021 Abstract Thiazolidinedione (TZD), a class of drugs that are mainly used to control type II diabetes mellitus (T2DM), acts fundamentally as a ligand of peroxisome proliferator-activated receptors (PPARs). Besides activating pathways responsible for glycemic control via enhancing insulin sensitivity and lipid homeostasis, activating PPARs leads to exciting other pathways related to bone formation, inflammation, and cell proliferation. Unfortunately, this diverse effect via activating several pathways may show in some studies adverse health outcomes as osteological, hepatic, cardiovascular, and carcinogenic effects. Thus, an argent demand is present to find and develop new active and potent antiglycemic drugs for the treatment of T2DM. To achieve this goal, the structure of TZD for research is considered as a leading structure domain. This review would guide future research in the design of novel TZD derivatives through highlighting the general modifications conducted to the structure component of TZD scaffold affecting their potency, binding efficacy, and selectivity for the control of type II diabetes mellitus.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2008/0058292 A1 Tawakol (43) Pub
    US 2008.0058292A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0058292 A1 Tawakol (43) Pub. Date: Mar. 6, 2008 (54) METHOD FOR INCREASING HDL AND A6II 3 L/455 (2006.01) HDL-2B LEVELS A6II 3 L/60 (2006.01) 76 ). A6IP 3/00 (2006.01) (76) Inventor: Raif Tawakol, Merced, CA (US) (52) U.S. Cl. ............................................ 514/161; 514/356 Correspondence Address: RONALD V. DAVIDGE 9900 STRLING ROAD (57) ABSTRACT SUTE 219 COOPER CITY, FL 33024 (US) The present invention provides a method for reducing flush (21) Appl. No.: 11/899,284 ing in a patient and for for increasing HDL and/or HDL-2b levels in a patient, with compositions being administered to 22) Filed: Sep.p 5, 2007 the ppatient onlyy twice a day,y from 30 to 60 minutes after lunch and 30 to 60 minutes after dinner. In some embodi Related U.S. Application Data ments, the compositions include an adipocyte G-protein (63) Continuation-in-part of application No. 10/977.508, antagonist, a PPAR-c. agonist , and a PPAR-y agonist in filed on Oct. 29, 2004. amounts effective in to provide a synergistic therapeutic HDL increasing effect, and/or a synergistic therapeutic (60) Provisional application No. 60/515,891, filed on Oct. HDL-2b increasing effect. 29, 2003. Publication Classification (51) Int. Cl. BREAKFAST LUNCH DINNER SLEEP Patent Application Publication Mar. 6, 2008 US 2008/0058292 A1 BREAKFAST LUNCH DINNER SLEEP FIG. 1 BREAKFAST LUNCH DINNER SLEEP FIG. 2 US 2008/0058292 A1 Mar. 6, 2008 METHOD FOR INCREASING HDL AND HDL-2B ingly, the combination of an adipocyte G-protein antagonist, LEVELS a peroxisome proliferator-activated receptor-C.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Role of Glitazars in Atherogenic Dyslipidemia and Diabetes: Two Birds with One Stone?
    Review Article Role of Glitazars in atherogenic dyslipidemia and diabetes: Two birds with one stone? Srinivasa P. Munigoti, C. V. Harinarayan1 Consultant Endocrinologist, Fortis Hospital, 1Director, Institute of Endocrinology, Diabetes and Osteoporosis, Sakra World Hospitals, Marathahalli, Bangalore, Karnataka, India ABSTRACT A triad of high triglycerides, low high-density lipoprotein (HDL) cholesterol, and elevated small dense low-density lipoprotein particles occurring in a patient with type 2 diabetes is referred to atherogenic diabetic dyslipidemia (ADD). Despite statin therapy, a signifi cant residual risk remains potentially attributable to increased triglyceride concentration and low HDL cholesterol, a characteristic hallmark of ADD. Current therapeutic options in reducing this residual risk include nicotinic acid, omega 3 fatty acids, and selective peroxisome proliferator-activated receptor-alpha (PPAR) agonists (fi brates). These drugs are limited in their potential either by lack of evidence to support their role in reducing cardiovascular events or due to their side effects. This review details their current status and also the role of new glitazar, saroglitazar adual PPARα/γ agonist with predominant PPARα activity in the management of ADD. Key words: Atherogenesis, diabetic dyslipidemia, proliferator-activated receptor-alphas, saroglitazar INTRODUCTION hydrolyzed by hepatic lipase orlipoprotein lipase resulting in low HDL; Apo A-I dissociates from thereduced-size A triad of high triglycerides, low high-density HDL, which is fi ltered by the renalglomeruli and degraded [2,3] lipoprotein (HDL) cholesterol and elevated small dense in renal tubular cells [Figure 1]. low-density lipoprotein (LDL) particles occurring in a Reducing LDL cholesterol (C) using statins is a proven patient with type 2 diabetes is referred to atherogenic strategy for primary as well as secondary prevention of diabetic dyslipidemia (ADD).
    [Show full text]