The aim of this study was to determine whether MetS has an impact on the global DNA methylation pattern and the DNA methylation of several genes related to adipogenesis (PPARG, PPARA), lipid metabolism (RXRA, SREBF2, SREBF1, SCD, LPL, LXRb), and inflammation (LRP1 C3, LEP and TNF) in visceral adipose tissue.
Peroxisome proliferator-activated receptor-γ (PPARγ) is a master regulator of adipogenesis, and alterations in its function are associated with various pathological processes related to metabolic syndrome.
The discovery that VCE-004.8, a dual PPARγ and CB<sub>2</sub> receptor agonist, also inhibits prolyl-hydroxylases (PHDs) and activates the HIF pathway provided a rationale to investigate its effect in in vitro models of adipogenesis and in a murine model of metabolic syndrome, all processes critically regulated by these targets of VCE-004.8.
We developed and tested a novel dual modulator, RB394, which acts as a soluble epoxide hydrolase (sEH) inhibitor and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist in rat models of the metabolic syndrome-the obese spontaneously hypertensive (SHROB) rat and the obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat.
Transcription factors (AMP-activated protein kinase-1, STAT3, sterol regulatory element-binding protein-1 and peroxisome proliferator-activated receptor-γ), leptin and adiponectin receptors seem to be the most promising molecular targets for the therapy of cancers associated with MS.
Associations between the components of metabolic syndrome and the polymorphisms in the peroxisome proliferator-activated receptor gamma (<i>PPAR-γ</i>), the fat mass and obesity-associated (<i>FTO</i>), and the melanocortin-4 receptor (<i>MC4R</i>) genes.
Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by PPARγ modulation.
Collectively, this study establishes a critical role of CRL4B in the regulation of PPARγ stability and insulin sensitivity and suggests that CUL4B could be a potential therapeutic target for combating obesity and metabolic syndromes.
Findings from the present study suggested that a sedentary lifestyle and vitamin D deficiency accelerated the occurrence of metabolic syndrome probably by decreasing the expression of nuclear receptor PPARγ.
The possible causes of metabolic syndrome by in-utero epigenetic alterations of genes involved in energy metabolism (PPARγ and PPARα), microRNAs, arginine methyltransferases, lysine demethylases, and histone deacetylaces have been elucidated.
The nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and its hetero-dimerization partner retinoid X receptor α (RXRα) are considered as drug targets in the treatment of diseases like the metabolic syndrome and diabetes mellitus type 2.
The identification of fibrates and TZDs as respective ligands for PPARα and PPARγ was a groundbreaking finding that sparked notable pharmaceutical interest in PPARs as potential drug targets for treatment of the metabolic syndrome.
The aim of this study was to investigate the association of C1431T and Pro12Ala polymorphisms of PPARγ gene and their haplotypes and diplotypes with risk of metabolic syndrome (MetS) in an Iranian population.
In the group of participants with PPARγPro12Ala or Ala12Ala genotypes, those with the LPL Pvu (-/+) or (+/+) genotype had greater odds for MetSy (odds ratio OR=5.98; 95% confidence interval CI: 1.46-24.47, p=0.013).