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.

引用

页码：809 / 823

页数：15

共 187 条

[41] Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events):: a randomised controlled trial [J].

Dormandy, JA ;

Charbonnel, B ;

Eckland, DJA ;

Erdmann, E ;

Massi-Benedetti, M ;

Kmoules, IK ;

Skene, AM ;

Tan, MH ;

Lefébvre, PJ ;

Murray, GD ;

Standl, E ;

Wilcox, RG ;

Wlhelmsen, L ;

Betteridge, J ;

Birkeland, K ;

Golay, A ;

Heine, RJ ;

Korányi, L ;

Laakso, M ;

Mokán, M ;

Norkus, A ;

Pirags, V ;

Podar, T ;

Scheen, A ;

Scherbaum, W ;

Schernthaner, G ;

Schmitz, O ;

Skrha, J ;

Smith, U ;

Taton, J .

LANCET, 2005, 366 (9493) :1279-1289

[42] Mitochondrial biogenesis and dynamics in the developing and diseased heart [J].

Dorn, Gerald W., II ;

Vega, Rick B. ;

Kelly, Daniel P. .

GENES & DEVELOPMENT, 2015, 29 (19) :1981-1991

[43] Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function [J].

Drosatos, Konstantinos ;

Pollak, Nina M. ;

Pol, Christine J. ;

Ntziachristos, Panagiotis ;

Willecke, Florian ;

Valenti, Mesele-Christina ;

Trent, Chad M. ;

Hu, Yunying ;

Guo, Shaodong ;

Aifantis, Iannis ;

Goldberg, Ira J. .

CIRCULATION RESEARCH, 2016, 118 (02) :241-253

[44] Peroxisome Proliferator-Activated Receptor-γ Activation Prevents Sepsis-Related Cardiac Dysfunction and Mortality In Mice [J].

Drosatos, Konstantinos ;

Khan, Raffay S. ;

Trent, Chad M. ;

Jiang, Hongfeng ;

Son, Ni-Huiping ;

Blaner, William S. ;

Homma, Shunichi ;

Schulze, P. Christian ;

Goldberg, Ira J. .

CIRCULATION-HEART FAILURE, 2013, 6 (03) :550-+

[45] Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-γ both induce cardiac hypertrophy in mice [J].

Duan, SZ ;

Ivashchenko, CY ;

Russell, MW ;

Milstone, DS ;

Mortensen, RM .

CIRCULATION RESEARCH, 2005, 97 (04) :372-379

[46] Distinct but complementary contributions of PPAR isotypes to energy homeostasis [J].

Dubois, Vanessa ;

Eeckhoute, Jerome ;

Lefebvre, Philippe ;

Staels, Bart .

JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (04) :1202-1214

[47] Complementary intestinal mucosa and microbiota responses to caloric restriction [J].

Duszka, Kalina ;

Ellero-Simatos, Sandrine ;

Ow, Ghim Siong ;

Defernez, Marianne ;

Paramalingam, Eeswari ;

Tett, Adrian ;

Ying, Shi ;

Koenig, Juergen ;

Narbad, Arjan ;

Kuznetsov, Vladimir A. ;

Guillou, Herve ;

Wahli, Walter .

SCIENTIFIC REPORTS, 2018, 8

[48] The Hypoxia-Inducible MicroRNA Cluster miR-199a∼214 Targets Myocardial PPARδ and Impairs Mitochondrial Fatty Acid Oxidation [J].

el Azzouzi, Hamid ;

Leptidis, Stefanos ;

Dirkx, Ellen ;

Hoeks, Joris ;

van Bree, Bianca ;

Brand, Karl ;

McClellan, Elizabeth A. ;

Poels, Ella ;

Sluimer, Judith C. ;

van den Hoogenhof, Maarten M. G. ;

Armand, Anne-Sophie ;

Yin, Xiaoke ;

Langley, Sarah ;

Bourajjaj, Meriem ;

Olieslagers, Serve ;

Krishnan, Jaya ;

Vooijs, Marc ;

Kurihara, Hiroki ;

Stubbs, Andrew ;

Pinto, Yigal M. ;

Krek, Wilhelm ;

Mayr, Manuel ;

Martins, Paula A. da Costa ;

Schrauwen, Patrick ;

De Windt, Leon J. .

CELL METABOLISM, 2013, 18 (03) :341-354

[49] Peroxisome Proliferator-activated Receptor (PPAR) Gene Profiling Uncovers Insulin-like Growth Factor-1 as a PPARα Target Gene in Cardioprotection [J].

el Azzouzi, Hamid ;

Leptidis, Stefanos ;

Bourajjaj, Meriem ;

Armand, Anne-Sophie ;

van der Nagel, Roel ;

van Bilsen, Marc ;

Martins, Paula A. Da Costa ;

De Windt, Leon J. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (16) :14598-14607

[50] TAZ Is a Negative Regulator of PPARγ Activity in Adipocytes and TAZ Deletion Improves Insulin Sensitivity and Glucose Tolerance [J].

El Ouarrat, Dalila ;

Isaac, Roi ;

Lee, Yun Sok ;

Oh, Da Young ;

Wollam, Joshua ;

Lackey, Denise ;

Riopel, Matthew ;

Bandyopadhyay, Gautam ;

Seo, Jong Bae ;

Sampath-Kumar, Revathy ;

Olefsky, Jerrold M. .

CELL METABOLISM, 2020, 31 (01) :162-+

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