PPAR control of metabolism and cardiovascular functions

被引：632
作者：
Montaigne, David [1 ]
Butruille, Laura [1 ]
Staels, Bart [1 ]
机构：
[1] Univ Lille, CHU Lille, INSERM, Inst Pasteur Lille,U1011 EGID, Lille, France
来源：
NATURE REVIEWS CARDIOLOGY | 2021年 / 18卷 / 12期
关键词：
ACTIVATED-RECEPTOR-ALPHA; LOW-DENSITY-LIPOPROTEIN; FATTY-ACID OXIDATION; WHITE ADIPOSE-TISSUE; MYOCARDIAL-METABOLISM; INSULIN-RESISTANCE; LIPID-METABOLISM; GENE-EXPRESSION; ISCHEMIA/REPERFUSION INJURY; CONTRACTILE DYSFUNCTION;
D O I：
10.1038/s41569-021-00569-6
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Novel peroxisome proliferator-activated receptor (PPAR) agonists are providing new opportunities in the management of metabolic and cardiovascular diseases. In this Review, Staels and colleagues discuss the physiological regulation and actions of the PPAR family and their modulation of the atherogenic lipid profile, atherosclerosis and cardiac remodelling. Peroxisome proliferator-activated receptor-alpha (PPAR alpha), PPAR delta and PPAR gamma are transcription factors that regulate gene expression following ligand activation. PPAR alpha increases cellular fatty acid uptake, esterification and trafficking, and regulates lipoprotein metabolism genes. PPAR delta stimulates lipid and glucose utilization by increasing mitochondrial function and fatty acid desaturation pathways. By contrast, PPAR gamma promotes fatty acid uptake, triglyceride formation and storage in lipid droplets, thereby increasing insulin sensitivity and glucose metabolism. PPARs also exert antiatherogenic and anti-inflammatory effects on the vascular wall and immune cells. Clinically, PPAR gamma activation by glitazones and PPAR alpha activation by fibrates reduce insulin resistance and dyslipidaemia, respectively. PPARs are also physiological master switches in the heart, steering cardiac energy metabolism in cardiomyocytes, thereby affecting pathological heart failure and diabetic cardiomyopathy. Novel PPAR agonists in clinical development are providing new opportunities in the management of metabolic and cardiovascular diseases.
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收藏
页码：809 / 823
页数：15
相关论文
共 187 条
[1]   Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial [J].
Araki, Eiichi ;
Yamashita, Shizuya ;
Arai, Hidenori ;
Yokote, Koutaro ;
Satoh, Jo ;
Inoguchi, Toyoshi ;
Nakamura, Jiro ;
Maegawa, Hiroshi ;
Yoshioka, Narihito ;
Tanizawa, Yukio ;
Watada, Hirotaka ;
Suganami, Hideki ;
Ishibashi, Shun .
DIABETES CARE, 2018, 41 (03) :538-546
[2]   The Failing Heart Relies on Ketone Bodies as a Fuel [J].
Aubert, Gregory ;
Martin, Ola J. ;
Horton, Julie L. ;
Lai, Ling ;
Vega, Rick B. ;
Leone, Teresa C. ;
Koves, Timothy ;
Gardell, Stephen J. ;
Krueger, Marcus ;
Hoppel, Charles L. ;
Lewandowski, E. Douglas ;
Crawford, Peter A. ;
Muoio, Deborah M. ;
Kelly, Daniel P. .
CIRCULATION, 2016, 133 (08) :698-705
[3]   Preferential Oxidation of Triacylglyceride-Derived Fatty Acids in Heart Is Augmented by the Nuclear Receptor PPARα [J].
Banke, Natasha H. ;
Wende, Adam R. ;
Leone, Teresa C. ;
O'Donnell, J. Michael ;
Abel, E. Dale ;
Kelly, Daniel P. ;
Lewandowski, E. Douglas .
CIRCULATION RESEARCH, 2010, 107 (02) :233-241
[4]   Peroxisome proliferator-activated receptor α activates transcription of the brown fat uncoupling protein-1 gene -: A link between regulation of the thermogenic and lipid oxidation pathways in the brown fat cell [J].
Barberá, MJ ;
Schlüter, A ;
Pedraza, N ;
Iglesias, P ;
Villarroya, F ;
Giralt, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (02) :1486-1493
[5]   Effects of PPARs Agonists on Cardiac Metabolism in Littermate and Cardiomyocyte-Specific PPAR-γ - Knockout (CM-PGKO) Mice [J].
Barbieri, Michelangela ;
Di Filippo, Clara ;
Esposito, Antonietta ;
Marfella, Raffaele ;
Rizzo, Maria Rosaria ;
D'Amico, Michele ;
Ferraraccio, Franca ;
Di Ronza, Cristina ;
Duan, Sheng Zhong ;
Mortensen, Richard M. ;
Rossi, Francesco ;
Paolisso, Giuseppe .
PLOS ONE, 2012, 7 (04)
[6]   Deactivation of peroxisome proliferator-activated receptor-α during cardiac hypertrophic growth [J].
Barger, PM ;
Brandt, JM ;
Leone, TC ;
Weinheimer, CJ ;
Kelly, DP .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (12) :1723-1730
[7]   PPARδ regulates multiple proinflammatory pathways to suppress atherosclerosis [J].
Barish, Grant D. ;
Atkins, Annette R. ;
Downes, Michael ;
Olson, Peter ;
Chong, Ling-Wa ;
Nelson, Mike ;
Zou, Yuhua ;
Hwang, Hoosang ;
Kang, Heonjoong ;
Curtiss, Linda ;
Evans, Ronald M. ;
Lee, Chih-Hao .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (11) :4271-4276
[8]   The PPARβ/δ Activator GW501516 Prevents the Down-Regulation of AMPK Caused by a High-Fat Diet in Liver and Amplifies the PGC-1α-Lipin 1-PPARα Pathway Leading to Increased Fatty Acid Oxidation [J].
Barroso, Emma ;
Rodriguez-Calvo, Ricardo ;
Serrano-Marco, Lucia ;
Astudillo, Alma M. ;
Balsinde, Jesus ;
Palomer, Xavier ;
Vazquez-Carrera, Manuel .
ENDOCRINOLOGY, 2011, 152 (05) :1848-1859
[9]  
Bartelds B, 2000, CIRCULATION, V102, P926, DOI 10.1161/01.CIR.102.8.926
[10]   Alterations of peroxisome proliferator-activated receptor δ activity affect fatty acid-controlled adipose differentiation [J].
Bastie, C ;
Luquet, S ;
Holst, D ;
Jehl-Pietri, C ;
Grimaldi, PA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (49) :38768-38773
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