Exploring PPAR Gamma and PPAR Alpha's Regulation Role in Metabolism via Epigenetics Mechanism

Abstract

Peroxisome proliferator-activated receptors (PPARs) belong to a family of nuclear receptors. To date, three types of PPARs, namely PPARα, PPARδ, and PPARγ, have been identified, demonstrating co-expression across numerous tissues. PPARγ is primarily distributed in adipose tissue, the colon, the immune system, and the retina, while PPARα is predominantly expressed in metabolic tissues such as brown adipose tissue, the liver, and the kidneys. Both PPARγ and PPARα play crucial roles in various cellular processes. Recent data suggest that the PPAR family, among other mechanisms, might also be regulated by epigenetic mechanisms. Our recent studies, alongside numerous others, have highlighted the pivotal roles of DNA methylation and histone modifications in the regulation of PPARγ and PPARα, implicating them in the deterioration of metabolic disorders via epigenetic mechanisms. This still not fully understood mechanism of regulation in the nuclear receptors family has been summarized and described in the present paper. The present review summarizes the available data on PPARγ and PPARα regulation via epigenetic mechanisms, elucidating the link between the development of metabolic disorders and the dysregulation of PPARγ and PPARα resulting from these mechanisms.

Keywords: DNA methylation; PPARA; PPARG; histone modifications; metabolic syndrome; obesity.

Figure 1

Main characteristic of two isoforms: PPARγ and PPARα. Their expression, function and the list of main ligands that activate the particular peroxisome proliferator are shown [18,36].

Figure 2

Schematic mechanism of epigenetic regulation involved in PPARγ and PPARγ expression and action, and their effects on cell metabolism. DNMT—DNA methyltransferases; HDAC—histone deacetylases; HMT—histone methylases, FGF21—Fibroblast growth factor 21; ELOVL6—ELOVL fatty acid elongase 6; FADS1—fatty acid desaturase 1; FGβ—fibrogen beta chain; IL-1β—interleukin 1 beta; IL-6—interleukin 6; SREBP—sterol regulatory element-binding protein 1; FABP4—fatty acid-binding protein 4; ADIPOQ—adiponectin; ADIPOR2—adiponectin receptor 2 (graph was prepared using PowerPoint software 2021).