{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:54:20Z","timestamp":1790834060519,"version":"4.1.0"},"reference-count":139,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Cariplo grant","award":["2015-0552"],"award-info":[{"award-number":["2015-0552"]}]},{"name":"Linea 2, Azione (Intramural grant) received by Universit\u00e0 degli Studi di Milano"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Therapeutic approaches to metabolic syndrome (MetS) are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs) are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs), blood glucose, and abdominal adiposity. PPARs may be classified into the \u03b1, \u03b2\/\u03b4 and \u03b3 subtypes. The PPAR-\u03b1 agonists, mainly fibrates (including newer molecules such as pemafibrate) and omega-3 fatty acids, are powerful TG-lowering agents. They mainly affect TG catabolism and, particularly with fibrates, raise the levels of high-density lipoprotein cholesterol (HDL-C). PPAR-\u03b3 agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-\u03b1\/\u03b4 agonists, e.g., elafibranor, have been designed to achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to the insulin-sensitizing and antihyperglycemic effects of glitazones. They also hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD) which is closely associated with the MetS. The PPAR system thus offers an important hope in the management of atherogenic dyslipidemias, although concerns regarding potential adverse events such as the rise of plasma creatinine, gallstone formation, drug\u2013drug interactions (i.e., gemfibrozil) and myopathy should also be acknowledged.<\/jats:p>","DOI":"10.3390\/ijms19041197","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T03:12:09Z","timestamp":1523848329000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":237,"title":["PPAR Agonists and Metabolic Syndrome: An Established Role?"],"prefix":"10.3390","volume":"19","author":[{"given":"Margherita","family":"Botta","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Audano","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran"},{"name":"Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran"},{"name":"School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Sirtori","sequence":"additional","affiliation":[{"name":"Centro Dislipidemie, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-3619","authenticated-orcid":false,"given":"Nico","family":"Mitro","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-7061","authenticated-orcid":false,"given":"Massimiliano","family":"Ruscica","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"De Carvalho Vidigal, F., Bressan, J., Babio, N., and Salas-Salvado, J. (2013). Prevalence of metabolic syndrome in Brazilian adults: A systematic review. BMC Public Health, 13.","DOI":"10.1186\/1471-2458-13-1198"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, R., Li, W., Lun, Z., Zhang, H., Sun, Z., Kanu, J.S., Qiu, S., Cheng, Y., and Liu, Y. (2016). Prevalence of metabolic syndrome in Mainland China: A meta-analysis of published studies. BMC Public Health, 16.","DOI":"10.1186\/s12889-016-2870-y"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1001\/jama.2015.4260","article-title":"Prevalence of the metabolic syndrome in the United States, 2003-2012","volume":"313","author":"Aguilar","year":"2015","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"National Cholesterol Education Program (NCEP), and Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA, 285, 2486\u20132497.","DOI":"10.1001\/jama.285.19.2486"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"237","DOI":"10.4158\/EP.9.S2.5","article-title":"American College of Endocrinology position statement on the insulin resistance syndrome","volume":"9","author":"Einhorn","year":"2003","journal-title":"Endocr. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0140-6736(05)67402-8","article-title":"The metabolic syndrome\u2014A new worldwide definition","volume":"366","author":"Alberti","year":"2005","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s12020-016-0939-0","article-title":"Proprotein convertase subtilisin\/kexin type 9 (PCSK9) and metabolic syndrome: Insights on insulin resistance, inflammation, and atherogenic dyslipidemia","volume":"54","author":"Ferri","year":"2016","journal-title":"Endocrine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1475-2840-5-20","article-title":"Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: Therapeutic options beyond statins","volume":"5","author":"Tenenbaum","year":"2006","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.pharmthera.2010.01.008","article-title":"Niacin and fibrates in atherogenic dyslipidemia: Pharmacotherapy to reduce cardiovascular risk","volume":"126","author":"Chapman","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/B978-0-12-800101-1.00007-7","article-title":"The roles of peroxisome proliferator-activated receptors in the metabolic syndrome","volume":"121","author":"Mansour","year":"2014","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1056\/NEJMra1503519","article-title":"Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis","volume":"377","author":"Diehl","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1517\/14740338.2013.741585","article-title":"Examining the safety of PPAR agonists\u2014Current trends and future prospects","volume":"12","author":"Bortolini","year":"2013","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"44K","DOI":"10.1016\/j.amjcard.2005.08.007","article-title":"Pharmacokinetic interactions between statins and fibrates","volume":"96","author":"Corsini","year":"2005","journal-title":"Am. J. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ejim.2015.01.002","article-title":"Risk identification and possible countermeasures for muscle adverse effects during statin therapy","volume":"26","author":"Magni","year":"2015","journal-title":"Eur. J. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1172\/JCI88894","article-title":"Distinct but complementary contributions of PPAR isotypes to energy homeostasis","volume":"127","author":"Dubois","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"653017","DOI":"10.1155\/2014\/653017","article-title":"PPARs Integrate the Mammalian Clock and Energy Metabolism","volume":"2014","author":"Chen","year":"2014","journal-title":"PPAR Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0005-2760(96)00066-5","article-title":"The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation","volume":"1302","author":"Schoonjans","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/83328","article-title":"The role of PPAR-gamma in macrophage differentiation and cholesterol uptake","volume":"7","author":"Moore","year":"2001","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/1098-1136(200103)33:3<191::AID-GLIA1018>3.0.CO;2-M","article-title":"PPAR delta agonists stimulate oligodendrocyte differentiation in tissue culture","volume":"33","author":"Saluja","year":"2001","journal-title":"Glia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.cmet.2015.02.016","article-title":"Lack of sterol regulatory element binding factor-1c imposes glial Fatty Acid utilization leading to peripheral neuropathy","volume":"21","author":"Cermenati","year":"2015","journal-title":"Cell Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1161\/01.CIR.98.19.2088","article-title":"Mechanism of action of fibrates on lipid and lipoprotein metabolism","volume":"98","author":"Staels","year":"1998","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1002\/j.1460-2075.1996.tb00918.x","article-title":"PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene","volume":"15","author":"Schoonjans","year":"1996","journal-title":"EMBO J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2337\/db07-1318","article-title":"Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men","volume":"57","author":"Riserus","year":"2008","journal-title":"Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bbrc.2005.12.011","article-title":"AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1","volume":"340","author":"Lee","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1172\/JCI6223","article-title":"Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting","volume":"103","author":"Kersten","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.molmet.2014.02.002","article-title":"Integrated physiology and systems biology of PPARalpha","volume":"3","author":"Kersten","year":"2014","journal-title":"Mol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"34036","DOI":"10.1074\/jbc.M109.051052","article-title":"Fenofibrate simultaneously induces hepatic fatty acid oxidation, synthesis, and elongation in mice","volume":"284","author":"Oosterveer","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1006\/bbrc.2001.5608","article-title":"Adaptive increase in pyruvate dehydrogenase kinase 4 during starvation is mediated by peroxisome proliferator-activated receptor alpha","volume":"287","author":"Wu","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/1043-2760(93)90048-J","article-title":"Peroxisome proliferator-activated receptors A link between endocrinology and nutrition?","volume":"4","author":"Keller","year":"1993","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/384039a0","article-title":"The PPARalpha-leukotriene B4 pathway to inflammation control","volume":"384","author":"Devchand","year":"1996","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1182\/blood-2002-06-1762","article-title":"Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C\/EBP-beta complex formation","volume":"101","author":"Kleemann","year":"2003","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1128\/IAI.67.7.3488-3493.1999","article-title":"Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia","volume":"67","author":"Hill","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1210\/endo.137.1.8536636","article-title":"Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat","volume":"137","author":"Braissant","year":"1996","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1074\/jbc.270.5.2367","article-title":"Cloning of a protein that mediates transcriptional effects of fatty acids in preadipocytes. Homology to peroxisome proliferator-activated receptors","volume":"270","author":"Amri","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/j.1432-1033.1996.00242.x","article-title":"Activation of gene transcription by prostacyclin analogues is mediated by the peroxisome-proliferators-activated receptor (PPAR)","volume":"235","author":"Hertz","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1388-1981(03)00071-4","article-title":"Nutritional regulation and role of peroxisome proliferator-activated receptor delta in fatty acid catabolism in skeletal muscle","volume":"1633","author":"Holst","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1096\/fj.03-0269fje","article-title":"Peroxisome proliferator-activated receptor delta controls muscle development and oxidative capability","volume":"17","author":"Luquet","year":"2003","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e232","DOI":"10.1038\/oncsis.2016.41","article-title":"PPAR-delta promotes survival of breast cancer cells in harsh metabolic conditions","volume":"5","author":"Wang","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_40","first-page":"463","article-title":"PPARbeta\/delta ligands as modulators of the inflammatory response","volume":"9","author":"Kilgore","year":"2008","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.tem.2012.05.001","article-title":"PPARs at the crossroads of lipid signaling and inflammation","volume":"23","author":"Wahli","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1161\/ATVBAHA.107.149815","article-title":"Suppression of pro-inflammatory adhesion molecules by PPAR-delta in human vascular endothelial cells","volume":"28","author":"Fan","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.2353\/ajpath.2010.091010","article-title":"Peroxisome proliferator-activated receptor {delta} regulates inflammation via NF-{kappa}B signaling in polymicrobial sepsis","volume":"177","author":"Zingarelli","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1016\/j.febslet.2010.06.010","article-title":"PPARgamma in adipocyte differentiation and metabolism\u2014Novel insights from genome-wide studies","volume":"584","author":"Siersbaek","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1210\/endo.135.2.8033830","article-title":"Peroxisome proliferator-activated receptor (PPAR) gamma: Adipose-predominant expression and induction early in adipocyte differentiation","volume":"135","author":"Chawla","year":"1994","journal-title":"Endocrinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2174\/1574888X10666150531173309","article-title":"Molecular Mechanisms of PPAR-gamma Governing MSC Osteogenic and Adipogenic Differentiation","volume":"11","author":"Zhuang","year":"2016","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.2337\/diab.37.11.1549","article-title":"Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob\/ob mice and Zucker fatty rats","volume":"37","author":"Fujiwara","year":"1988","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1172\/JCI10843","article-title":"Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists","volume":"106","author":"Olefsky","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S1097-2765(00)80210-5","article-title":"PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance","volume":"4","author":"Kubota","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S1097-2765(00)80209-9","article-title":"PPAR gamma is required for placental, cardiac, and adipose tissue development","volume":"4","author":"Barak","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1172\/JCI8538","article-title":"Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency","volume":"105","author":"Miles","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/3099","article-title":"A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity","volume":"20","author":"Deeb","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2941","DOI":"10.1101\/gad.1709008","article-title":"PPARgamma and C\/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale","volume":"22","author":"Lefterova","year":"2008","journal-title":"Genes Dev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nature05894","article-title":"Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance","volume":"447","author":"Odegaard","year":"2007","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1128\/MCB.01651-09","article-title":"Cell-specific determinants of peroxisome proliferator-activated receptor gamma function in adipocytes and macrophages","volume":"30","author":"Lefterova","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1475-2840-9-64","article-title":"PPARgamma activation attenuates T-lymphocyte-dependent inflammation of adipose tissue and development of insulin resistance in obese mice","volume":"9","author":"Hartge","year":"2010","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s11748-015-0576-1","article-title":"PPAR-gamma agonist attenuates inflammation in aortic aneurysm patients","volume":"63","author":"Motoki","year":"2015","journal-title":"Gen. Thorac. Cardiovasc. Surg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1742-2094-9-63","article-title":"The PPAR-gamma agonist pioglitazone protects cortical neurons from inflammatory mediators via improvement in peroxisomal function","volume":"9","author":"Gray","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"894","DOI":"10.2174\/1381612822666161006151134","article-title":"PPAR Agonists, Atherogenic Dyslipidemia and Cardiovascular Risk","volume":"23","author":"Nikolic","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.2337\/db16-0046","article-title":"Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol","volume":"65","author":"Xiao","year":"2016","journal-title":"Diabetes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.ahj.2007.07.011","article-title":"The role of fibrates in the prevention of cardiovascular disease\u2014A pooled meta-analysis of long-term randomized placebo-controlled clinical trials","volume":"154","author":"Saha","year":"2007","journal-title":"Am. Heart J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/S0140-6736(05)67667-2","article-title":"Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial","volume":"366","author":"Keech","year":"2005","journal-title":"Lancet"},{"key":"ref_63","first-page":"241","article-title":"Mechanisms of action of absorbable hypolipidemic drugs","volume":"183","author":"Sirtori","year":"1985","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1016\/S0140-6736(06)68500-0","article-title":"The FIELD study","volume":"367","author":"Sirtori","year":"2006","journal-title":"Lancet"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1001\/jamacardio.2016.4828","article-title":"Association of Fenofibrate Therapy With Long-term Cardiovascular Risk in Statin-Treated Patients With Type 2 Diabetes","volume":"2","author":"Elam","year":"2017","journal-title":"JAMA Cardiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/13543784.2017.1312339","article-title":"PPAR-alpha agonists are still on the rise: An update on clinical and experimental findings","volume":"26","author":"Ferri","year":"2017","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Simental-Mendia, L.E., Simental-Mendia, M., Sanchez-Garcia, A., Banach, M., Atkin, S.L., Gotto, A.M., and Sahebkar, A. (2017). Effect of fibrates on glycemic parameters: A systematic review and meta-analysis of randomized placebo-controlled trials. Pharmacol. Res., in press.","DOI":"10.1016\/j.phrs.2017.12.030"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/1475-2840-11-140","article-title":"Balanced pan-PPAR activator bezafibrate in combination with statin: Comprehensive lipids control and diabetes prevention?","volume":"11","author":"Tenenbaum","year":"2012","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0140-6736(98)10364-1","article-title":"Medical significance of peroxisome proliferator-activated receptors","volume":"354","author":"Vamecq","year":"1999","journal-title":"Lancet"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1161\/CIRCULATIONAHA.104.475673","article-title":"Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets","volume":"115","author":"Brown","year":"2007","journal-title":"Circulation"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"547","DOI":"10.2337\/dc08-1809","article-title":"Antidiabetic action of bezafibrate in a large observational database","volume":"32","author":"Flory","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"754","DOI":"10.5551\/jat.28720","article-title":"Transcriptome Analysis of K-877 (a Novel Selective PPARalpha Modulator (SPPARMalpha))-Regulated Genes in Primary Human Hepatocytes and the Mouse Liver","volume":"22","author":"Tanaka","year":"2015","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1007\/s40265-017-0818-x","article-title":"Pemafibrate: First Global Approval","volume":"77","author":"Blair","year":"2017","journal-title":"Drugs"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"538","DOI":"10.2337\/dc17-1589","article-title":"Effects of Pemafibrate, a Novel Selective PPARalpha Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial","volume":"41","author":"Araki","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Sahebkar, A., Simental-Mendia, L.E., Mikhailidis, D.P., Pirro, M., Banach, M., Sirtori, C.R., Ruscica, M., and Reiner, Z. (2018). Effect of statin therapy on plasma apolipoprotein CIII concentrations: A systematic review and meta-analysis of randomized controlled trials. J. Clin. Lipidol., in press.","DOI":"10.1016\/j.jacl.2018.01.008"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jacl.2017.10.006","article-title":"Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor alpha modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial","volume":"12","author":"Ishibashi","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Arai, H., Yamashita, S., Yokote, K., Araki, E., Suganami, H., Ishibashi, S., and Group, K.S. (2018). Efficacy and Safety of Pemafibrate Versus Fenofibrate in Patients with High Triglyceride and Low HDL Cholesterol Levels: A Multicenter, Placebo-Controlled, Double-Blind, Randomized Trial. J. Atheroscler. Thromb.","DOI":"10.5551\/jat.44412"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.atherosclerosis.2017.04.013","article-title":"Phase 2 clinical trials with K-877 (pemafibrate): A promising selective PPAR-alpha modulator for treatment of combined dyslipidemia","volume":"261","author":"Camejo","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.atherosclerosis.2017.03.032","article-title":"Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia","volume":"261","author":"Arai","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-319-09665-0_1","article-title":"Structure of HDL: Particle subclasses and molecular components","volume":"224","author":"Kontush","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12933-017-0602-y","article-title":"Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator for management of atherogenic dyslipidaemia","volume":"16","author":"Fruchart","year":"2017","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_82","unstructured":"NCT03071692 (2018, April 13). Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts with diabeTes (PROMINENT), Available online: https:\/\/www.clinicaltrials.gov\/ct2\/results?cond=&term=NCT03071692&cntry=&state=&city=&dist=."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/j.1365-2362.1993.tb01286.x","article-title":"Fraudulent (and non fraudulent) fatty acids for human health","volume":"23","author":"Sirtori","year":"1993","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ceb.2015.02.003","article-title":"Acetyl-CoA and the regulation of metabolism: Mechanisms and consequences","volume":"33","author":"Shi","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"592S","DOI":"10.3945\/jn.111.155259","article-title":"Mechanisms of action of (n-3) fatty acids","volume":"142","author":"Calder","year":"2012","journal-title":"J. Nutr."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1096\/fj.11-194019","article-title":"Sustained activation of PPARalpha by endogenous ligands increases hepatic fatty acid oxidation and prevents obesity in ob\/ob mice","volume":"26","author":"Huang","year":"2012","journal-title":"FASEB J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.cell.2010.07.041","article-title":"GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects","volume":"142","author":"Oh","year":"2010","journal-title":"Cell"},{"key":"ref_88","first-page":"2129","article-title":"Update on the management of severe hypertriglyceridemia\u2014Focus on free fatty acid forms of omega-3","volume":"9","author":"Pirillo","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1016\/j.ijcard.2013.06.040","article-title":"Omega-3 polyunsaturated fatty acids in the treatment of hypertriglyceridaemia","volume":"170","author":"Pirillo","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s11883-017-0700-z","article-title":"Review of Cardiometabolic Effects of Prescription Omega-3 Fatty Acids","volume":"19","author":"Burke","year":"2017","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1185\/03007995.2015.1120190","article-title":"History and future of omega-3 fatty acids in cardiovascular disease","volume":"32","author":"Sperling","year":"2016","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Pizzini, A., Lunger, L., Demetz, E., Hilbe, R., Weiss, G., Ebenbichler, C., and Tancevski, I. (2017). The Role of Omega-3 Fatty Acids in Reverse Cholesterol Transport: A Review. Nutrients, 9.","DOI":"10.3390\/nu9101099"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1136\/jim-2017-000535","article-title":"Adipose tissue inflammation in insulin resistance: Review of mechanisms mediating anti-inflammatory effects of omega-3 polyunsaturated fatty acids","volume":"65","author":"Pahlavani","year":"2017","journal-title":"J. Investig. Med."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Kuda, O., Rossmeisl, M., and Kopecky, J. (2018). Omega-3 fatty acids and adipose tissue biology. Mol. Aspects Med., in press.","DOI":"10.1016\/j.mam.2018.01.004"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bbrc.2017.03.001","article-title":"GPR120 in adipocytes has differential roles in the production of pro-inflammatory adipocytokines","volume":"486","author":"Hasan","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00394-015-0834-0","article-title":"Mice fed fish oil diet and upregulation of brown adipose tissue thermogenic markers","volume":"55","author":"Bargut","year":"2016","journal-title":"Eur. J. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"13479","DOI":"10.1038\/ncomms13479","article-title":"The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes","volume":"7","author":"Cereijo","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1093\/ajcn\/59.2.384","article-title":"Elevated concentrations of plasma omega-3 polyunsaturated fatty acids among Alaskan Eskimos","volume":"59","author":"Parkinson","year":"1994","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.plefa.2015.11.001","article-title":"Brown but not white adipose cells synthesize omega-3 docosahexaenoic acid in culture","volume":"104","author":"Qin","year":"2016","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.numecd.2016.12.005","article-title":"Translating the biology of adipokines in atherosclerosis and cardiovascular diseases: Gaps and open questions","volume":"27","author":"Ruscica","year":"2017","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3945\/jn.114.205443","article-title":"Fish-oil-derived n-3 PUFAs reduce inflammatory and chemotactic adipokine-mediated cross-talk between co-cultured murine splenic CD8+ T cells and adipocytes","volume":"145","author":"Monk","year":"2015","journal-title":"J. Nutr."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1089\/met.2014.0137","article-title":"Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester): Effects Upon High-Sensitivity C-Reactive Protein and Lipid Parameters in Patients With Metabolic Syndrome","volume":"13","author":"Bays","year":"2015","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Buoite Stella, A., Gortan Cappellari, G., Barazzoni, R., and Zanetti, M. (2018). Update on the Impact of Omega 3 Fatty Acids on Inflammation, Insulin Resistance and Sarcopenia: A Review. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010218"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1007\/s11883-011-0210-3","article-title":"Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: A systematic review and meta-analysis","volume":"13","author":"Wei","year":"2011","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s40256-016-0170-7","article-title":"Omega-3 Fatty Acid Formulations in Cardiovascular Disease: Dietary Supplements are Not Substitutes for Prescription Products","volume":"16","author":"Fialkow","year":"2016","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jacl.2017.10.012","article-title":"Omega-3 carboxylic acids in patients with severe hypertriglyceridemia: EVOLVE II, a randomized, placebo-controlled trial","volume":"12","author":"Stroes","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jacl.2013.10.003","article-title":"Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: The EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial","volume":"8","author":"Kastelein","year":"2014","journal-title":"J. Clin. Lipidol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1016\/j.clinthera.2013.07.420","article-title":"A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial)","volume":"35","author":"Maki","year":"2013","journal-title":"Clin. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"GISSI-Prevenzione Investigators (1999). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell\u2019Infarto miocardico. Lancet, 354, 447\u2013455.","DOI":"10.1016\/S0140-6736(99)07072-5"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/S0140-6736(07)60527-3","article-title":"Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis","volume":"369","author":"Yokoyama","year":"2007","journal-title":"Lancet"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1056\/NEJMoa1003603","article-title":"n-3 fatty acids and cardiovascular events after myocardial infarction","volume":"363","author":"Kromhout","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1001\/jamacardio.2017.5205","article-title":"Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77917 Individuals","volume":"3","author":"Aung","year":"2018","journal-title":"JAMA Cardiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/clc.22692","article-title":"Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial","volume":"40","author":"Bhatt","year":"2017","journal-title":"Clin. Cardiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.phrs.2016.11.005","article-title":"Non-insulin anti-diabetic drugs: An update on pharmacological interactions","volume":"115","author":"Ruscica","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1056\/NEJMoa072761","article-title":"Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes","volume":"356","author":"Nissen","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1001\/archinternmed.2010.207","article-title":"Rosiglitazone revisited: An updated meta-analysis of risk for myocardial infarction and cardiovascular mortality","volume":"170","author":"Nissen","year":"2010","journal-title":"Arch. Intern. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1001\/jama.298.10.1180","article-title":"Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials","volume":"298","author":"Lincoff","year":"2007","journal-title":"JAMA"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/j.1472-8206.2009.00741.x","article-title":"CHICAGO, PERISCOPE and PROactive: CV risk modification in diabetes with pioglitazone","volume":"23","author":"Betteridge","year":"2009","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1001\/jama.299.13.1561","article-title":"Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: The PERISCOPE randomized controlled trial","volume":"299","author":"Nissen","year":"2008","journal-title":"JAMA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jacc.2010.06.055","article-title":"Lowering the triglyceride\/high-density lipoprotein cholesterol ratio is associated with the beneficial impact of pioglitazone on progression of coronary atherosclerosis in diabetic patients: Insights from the PERISCOPE (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) study","volume":"57","author":"Nicholls","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1001\/jama.296.21.joc60158","article-title":"Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: A randomized trial","volume":"296","author":"Mazzone","year":"2006","journal-title":"JAMA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1161\/CIRCULATIONAHA.107.746610","article-title":"Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus","volume":"117","author":"Davidson","year":"2008","journal-title":"Circulation"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1056\/NEJMoa1506930","article-title":"Pioglitazone after Ischemic Stroke or Transient Ischemic Attack","volume":"374","author":"Kernan","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.2337\/dc16-0798","article-title":"Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease","volume":"39","author":"Inzucchi","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_125","first-page":"914","article-title":"Pioglitazone and Risk for Bone Fracture: Safety Data from a Randomized Clinical Trial","volume":"102","author":"Viscoli","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.phrs.2016.02.028","article-title":"PPARgamma signaling and emerging opportunities for improved therapeutics","volume":"111","author":"Wang","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Palomer, X., Barroso, E., Pizarro-Delgado, J., Pena, L., Botteri, G., Zarei, M., Aguilar, D., Montori-Grau, M., and Vazquez-Carrera, M. (2018). PPARbeta\/delta: A Key Therapeutic Target in Metabolic Disorders. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030913"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1517\/14656566.2014.876992","article-title":"New peroxisome proliferator-activated receptor agonists: Potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease","volume":"15","author":"Sahebkar","year":"2014","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/hep.26461","article-title":"Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha\/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis","volume":"58","author":"Staels","year":"2013","journal-title":"Hepatology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.2337\/dc11-0093","article-title":"Effects of the new dual PPAR alpha\/delta agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism","volume":"34","author":"Cariou","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1053\/j.gastro.2016.01.038","article-title":"Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis without Fibrosis Worsening","volume":"150","author":"Ratziu","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"7706","DOI":"10.1038\/srep07706","article-title":"Observational study of effects of Saroglitazar on glycaemic and lipid parameters on Indian patients with type 2 diabetes","volume":"5","author":"Chatterjee","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1136\/gutjnl-2016-312431","article-title":"Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease","volume":"66","author":"Rotman","year":"2017","journal-title":"Gut"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1089\/dia.2013.0253","article-title":"A multicenter, prospective, randomized, double-blind study to evaluate the safety and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes mellitus patients having hypertriglyceridemia not controlled with atorvastatin therapy (PRESS VI)","volume":"16","author":"Jani","year":"2014","journal-title":"Diabetes Technol. Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.phrs.2007.03.002","article-title":"PPAR dual agonists: Are they opening Pandora\u2019s Box?","volume":"56","author":"Balakumar","year":"2007","journal-title":"Pharmacol. Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1080\/07853890.2017.1366042","article-title":"Nutraceutical approaches to metabolic syndrome","volume":"49","author":"Sirtori","year":"2017","journal-title":"Ann. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/eurheartj\/ehx659","article-title":"Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology\/European Atherosclerosis Society guidelines: A contemporary population-based study","volume":"39","author":"Madsen","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.phrs.2017.12.028","article-title":"Present therapeutic role of cholesteryl ester transfer protein inhibitors","volume":"128","author":"Ferri","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1161\/ATVBAHA.118.310727","article-title":"Is It Time for New Thinking about High-Density Lipoprotein?","volume":"38","author":"Madsen","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/4\/1197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:00:43Z","timestamp":1760194843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/4\/1197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,14]]},"references-count":139,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4]]}},"alternative-id":["ijms19041197"],"URL":"https:\/\/doi.org\/10.3390\/ijms19041197","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,14]]}}}