PPARs and Metabolic Syndrome

Peroxisome proliferator-activated receptors (PPARs) exert versatile biological effects, notably in energy metabolism. During the last two decades, numerous studies have demonstrated that PPARs act as pivotal regulators of metabolic syndrome, a series of disorders in energy utilization and storage that are implicated with type 2 diabetes, diabetic nephropathy, and cardiovascular diseases, to mention a few. PPARí µí»¼ and PPARí µí»¾ are the molecular targets of a number of marketed drugs for the treatment of these diseases, and accumulating evidence suggested PPARí µí»½/í µí»¿ as a potential therapeutic drug target as well. Although energy metabolism and metabolic syndrome are the most intensively studied domain of PPARs, it has not been addressed specifically in any issue of PPAR Research ever since its launch. Here, we gathered 3 reviews and 5 research articles that encompass metabolic syndrome and its complications. M. Aprile et al. tackled the subject of PPARí µí»¾ and human adipogenesis in their research article. Rather than focusing on canonical PPARí µí»¾ transcripts, authors largely emphasized on the critical contribution of PPARí µí»¾ dominant negative isoforms to adipogenesis and their implied potential role in pathological conditions. In addition, a novel of PPARí µí»¾ dominant negative transcript, í µí»¾1ORF4, was first identified in this study. In regard to nonalcoholic fatty liver diseases, the hepatic expression of the metabolic syndrome, M. Sharif et al. conducted a thorough analysis of previously published data about the steatogenic role of PPARí µí»¾ and summarized two probable PPARí µí»¾ ligand-dependent toxicological modes of action: (i) activation of PPARí µí»¾ in hepatocytes and (ii) inhibition in adipocytes. Two papers, one review and a research article, by Z. Jia and Y. Sun et al., appraised the role of PPARí µí»¾ in diabetic nephropathy (DN). Their comprehensive review summarized the limitations of traditional PPARí µí»¾ agonists, addressed the advantages of newly developed PPARí µí»¾ agonists, and rendered new insights into the therapeutic potential of PPARí µí»¾ agonists in the treatment of DN, while the research article suggested that a combination of PPARí µí»¾ agonists with COX-2/PGE2 inhibitors may be an alternative way of dealing with DN. In another research article, J. Jin et al. analyzed the correlation between PPAR gene polymorphisms and pediatric primary nephrotic syndrome (PNS) by comparing children with PNS against healthy subjects. They found that PPARí µí»¾ (Pro12Ala) and PGC-1í µí»¼ (Gly482Ser) polymorphisms are associated with abnormal insulin and triglyceride metabolism in pediatric PNS patients, suggesting that …