The obtained results allow considering this compound as an interesting lead for the development of a new class of PPAR pan-agonists endowed with an activation profile exploitable for therapy of metabolic syndrome.
Nowadays, novel PPARα drugs with broad safety margins and therapeutic potential for metabolic syndrome and cardiovascular diseases are being developed and applied in the clinical setting.
Supportingly, antibiotics prevented both downregulation of PPAR genes and the development of metabolic syndrome, while PPAR agonists prevented development of metabolic syndrome in TLR4<sup>ΔIEC</sup> mice.
Low dose of clinical fibrates was effective against MS development independent of PPARα, and this action was mediated by STAT3 signalling inhibition in adipose tissue and, to a lesser extent, in hepatic tissues.
The aim of this study was to establish associations between MetS-related abnormalities and the <i>PPAR-γ</i> rs1801282, <i>FTO</i> rs9939609, and <i>MC4R</i> rs17782313 polymorphisms.
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.
Finally, the miR-21/PPARα axis was found amplified in liver and muscle biopsies, and in serum, of NAFLD patients, co-substantiating its role in the development of the metabolic syndrome.
The available relatives of the same family were interviewed (DSM-IV-R) and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS), leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs) for the leptin receptor and promoter and PPAR-γ2 genes.
Taken together, these findings indicate that IGFBP-2 might be a new target of metformin action in diabetes and the metformin-AMPK-Sirt1-PPARα-IGFBP-2 network may provide a novel pathway that could be applied to ameliorate metabolic syndromes by controlling IGF-1 bioavailability.
All PPAR SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malaysia, where only PPARα V162 and PPARγ2 T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively.
The objective of this chapter is to highlight the therapeutic benefits of targeting more than one PPAR subtype in the treatment of the metabolic syndrome.
Our results point to the use of PPAR and NR4A mRNA levels in the overall peripheral blood mononuclear cells as biomarkers of Metabolic Syndrome and bona fide putative targets of pharmacological therapy.
In previous studies, Pro12Ala polymorphism in peroxisome proliferator- activated receptors gamma 2 (PPAR-γ2) was shown to be associated with both longevity and metabolic syndrome, which was closely related with hyperuricemia.
The frequency distribution of rare alleles for PPARα (L162V) and PPARγ (P12A and H449H) was compared using the chi square test in 363 HIV-1-infected patients classified according to the presence or absence of the metabolic syndrome after 48 months of follow-up on their first PI-containing regimen.
The high potency, significant gene induction, excellent PK profiles, and good in vivo efficacies in three animal models may render compound 24 as a valuable pharmacological tool in elucidating the complex roles of PPARalpha/delta dual agonists and as a potential treatment of the metabolic syndrome.
In conclusion, the PPARalpha-L162V polymorphism alone or in interaction with dietary fat intake is associated with components of the metabolic syndrome.