PPAR control of metabolism and cardiovascular functions

Abstract

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 improving insulin sensitivity and glucose metabolism. PPARs also exert anti-atherogenic and anti-inflammatory effects on the vascular wall and immune cells. Clinically, PPARγ activation by glitazones and PPARα activation by fibrates improve 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.

Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis

“…The AMPK link was demonstrated between exercise and mitochondrial turnover with mitophagy activation, which helped refreshing the mitochondrial pool [98]. The effect of exercise, such as that of statins, can be considered as hormetic, since it causes transient elevation of ROS stimulating mitochondrial biogenesis and function (a process known as mitohormesis) but also improves mitophagy [99,100]. The increasing incidence of cardiovascular disorders can be attributed, at least partially, to the lack of exercise, which stimulates mitochondrial function, resulting in anti-inflammatory effect.…”

Schisandrin B regulates macrophage polarization and alleviates liver fibrosis via activation of PPARγ

“…In our study, H&E, Masson's trichrome, and Sirius red staining clearly reflected that Sch B could attenuate chronic liver injury and liver fibrosis, which indicated that Sch B is a potential compound for treating liver fibrosis. PPARγ is a nuclear receptor known for regulating glucose and lipid metabolism disorders (28,29). PPARγ also exerts antiinflammatory effects on immune cells (30).…”

Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors

“…The essential transcription factor governing adipocyte biology is thought to be PPARγ [ 63 , 64 ]. Detailed information about PPARγ can be found in several excellent reviews [ 65 , 66 ]. In the present paper, we focus on the functions of PPARγ in adipose tissue in vivo.…”