PPAR control of metabolism and cardiovascular functions.
David MontaigneLaura ButruilleBart StaelsPublished in: Nature reviews. Cardiology (2021)
Peroxisome proliferator-activated receptor-α (PPARα), PPARδ and PPARγ are transcription factors that regulate gene expression following ligand activation. PPARα increases cellular fatty acid uptake, esterification and trafficking, and regulates lipoprotein metabolism genes. PPARδ stimulates lipid and glucose utilization by increasing mitochondrial function and fatty acid desaturation pathways. By contrast, PPARγ 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, PPARγ activation by glitazones and PPARα 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.
Keyphrases
- fatty acid
- insulin resistance
- heart failure
- gene expression
- adipose tissue
- type diabetes
- cardiovascular disease
- skeletal muscle
- metabolic syndrome
- anti inflammatory
- magnetic resonance imaging
- computed tomography
- polycystic ovary syndrome
- high fat diet induced
- weight loss
- contrast enhanced
- blood glucose
- genome wide identification