PPAR agonists and metabolic syndrome: An established role?

Botta, M. and Audano, M. and Sahebkar, A. and Sirtori, C. R. and Mitro, N. and Ruscica, M. (2018) PPAR agonists and metabolic syndrome: An established role? International Journal of Molecular Sciences, 19 (4).

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Abstract

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 α, β/δ and γ subtypes. The PPAR-α 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-γ agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-α/δ 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-drug interactions (i.e., gemfibrozil) and myopathy should also be acknowledged. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Additional Information: Cited By :25 Export Date: 16 February 2020 Correspondence Address: Mitro, N.; Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di MilanoItaly; email: nico.mitro@unimi.it
Uncontrolled Keywords: Elafibrinor Metabolic syndrome Pemafibrate PPARs alanine aminotransferase apolipoprotein A1 apolipoprotein A2 apolipoprotein C3 bezafibrate C reactive protein CCAAT enhancer binding protein alpha CCAAT enhancer binding protein beta creatinine elafibranor gelatinase B gemfibrozil glitazone derivative high density lipoprotein cholesterol icosapentaenoic acid immunoglobulin enhancer binding protein interleukin 6 lipoprotein messenger RNA omega 3 fatty acid peroxisome proliferator activated receptor peroxisome proliferator activated receptor alpha peroxisome proliferator activated receptor delta peroxisome proliferator activated receptor gamma telmisartan triacylglycerol tumor necrosis factor unindexed drug 2 methyl 4 4 methyl 2 (4 trifluoromethylphenyl) 5 thiazolylmethylthio]phenoxy]acetic acid 4 2 (3 fluoro 4 trifluoromethylphenyl) 4 methyl 5 thiazolylmethylthio] 2 methylphenoxy]acetic acid (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid 2,4 thiazolidinedione derivative 2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid antidiabetic agent antilipemic agent benzoxazole derivative butyric acid derivative chalcone derivative lipid propionic acid derivative abdominal obesity blood pressure concentration (parameters) gene expression glucose blood level homeostasis human inflammation intracellular signaling lipogenesis metabolic syndrome X nonalcoholic fatty liver nonhuman phase 1 clinical trial (topic) phase 2 clinical trial (topic) phase 3 clinical trial (topic) protein expression Review agonists animal blood chemistry drug development drug effect insulin resistance lipid metabolism metabolism Animals Benzoxazoles Butyrates Chalcones Drug Discovery Humans Hypoglycemic Agents Hypolipidemic Agents Lipids Peroxisome Proliferator-Activated Receptors Propionates Thiazolidinediones Triglycerides
Subjects: WD Nutrition Disease and metabolic diseases
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 26 May 2020 07:04
Last Modified: 26 May 2020 07:04
URI: http://eprints.mums.ac.ir/id/eprint/17245

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