PPARs: Regulators of Metabolism and As Therapeutic Targets in Cardiovascular disease. Part II: PPAR-β/δ and PPAR-γ

Abstract

The PPARs are a subfamily of three ligand-inducible transcription factors, which belong to the superfamily of nuclear hormone receptors. In mammals, the PPAR subfamily consists of three members: PPAR-α, PPAR-β/δ and PPAR-γ. PPARs control the expression of a large number of genes involved in metabolic homeostasis, lipid, glucose and energy metabolism, adipogenesis and inflammation. PPARs regulate a large number of metabolic pathways that are implicated in the pathogenesis of metabolic diseases such as metabolic syndrome, Type 2 diabetes mellitus, nonalcoholic fatty liver disease and cardiovascular disease. The aim of this review is to provide up-to-date information about the biochemical and metabolic actions of PPAR-β/δ and PPAR-γ, the therapeutic potential of their agonists currently under clinical development and the cardiovascular disease outcome of clinical trials of PPAR-γ agonists, pioglitazone and rosiglitazone.

Ginsenoside Rg3 Alleviates ox-LDL Induced Endothelial Dysfunction and Prevents Atherosclerosis in ApoE−/− Mice by Regulating PPARγ/FAK Signaling Pathway

“…Research on the variance in gene expression profiles in the renal cortex of diabetic nephropathy rats treated with Rg3 showed that the PPAR signaling pathway was predominantly altered, indicating that PPAR is involved in mechanisms underlying Rg3 improving diabetic nephropathy (Wang et al, 2016). Evidence showed that PPARg may also involve in lipid metabolism (Han et al, 2017), the obesity associated with chronic hypoxia can lead to severe endothelium-dependent diastolic dysfunction, resulting in obstructive sleep apnea (OSA), whereas the PPARg agonist can significantly improve endothelial diastolic function and thus inhibit OSA (Zhang et al, 2017). Thus, whether Rg3 have effects on regulating PPARg in dyslipidemia induced AS which interfere FAK-related pathways or not have yet to be explored.…”

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

“…PPARα upregulates lipid uptake and β-oxidation of fatty acids, whereas PPARγ promotes adipocyte differentiation and adipokine production in adipose tissues to improve insulin sensitivity in diabetic patients [45][46][47]. Owing to these physiological functions in energy metabolism, PPARs are the molecular targets of metabolic disorders [48]. To assess the PPAR isoform specificity of 1 and 2, three reporter cell lines expressing luciferase genes in response to PPARα, PPARβ/δ, and PPARγ agonists were used [49].…”

Pioglitazone and PPAR-γ modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study

“…Furthermore, the current study revealed that IS patients without CKD or concurrent telmisartan use for BP control may have trends of obtaining more benefits when taking pioglitazone for T2DM. It is well known that PPAR-γ may have metabolism regulating and neuroprotective effects and could have protective effects for HTN, atherosclerosis and CKD [5,6,35]. Pioglitazone, a potent PPAR-γ agonist, has demonstrated vascular protective effects in previous studies [7,8,11].…”

“…Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a known essential mediator for the maintenance of whole body insulin sensitivity [5]. Biochemical and metabolic regulators of PPAR-γ have been considered as therapeutic targets in cardiovascular diseases [6]. A previous Cochrane review demonstrated that PPAR-γ agonists may improve insulin sensitivity and probably reduce recurrent strokes and total cardiovascular death events [4].…”