Peroxisome proliferator-activated receptor-y PPAR

The thiazolidinediones have also been reported to act as inhibitors of the respiratory chain at high concentrations, and this appears to account for their ability to activate AMGPK in cultured cells. However, the primary target of the thiazolidinediones appears to be the peroxisome proliferator-activated receptor-y ( PPAR-y), a member of the nuclear receptor superfamily expressed in adipocytes. One of the major effects of stimulation of PPAR-y in adipocytes is the release ofthe... 

Thiazolidinediones are the newer agents that favourably influence insulin sensitivity and possibly also pancreatic fS-cell function. The biological response of thiazolidinediones is mediated by binding to the nuclear peroxisome proliferator-activated receptor-y (PPAR)... 

The Glaxo group tvas the first to report the structure of a heterodimeric complex between two activated NHRs (peroxisome proliferator-activated receptor-y) PPAR-y and (retinoid X receptor-a) RXR-a. The structure (PDB entry 1FM6) of this heterodimer complex contains six components the two receptor LBDs, their two respective ligands, and two peptides derived from the steroid receptor co-activator-1 (SRC-1). These peptides contain a conserved LxxLL motif that is present in this class of co-activators. The complex is butterfly shaped, with both LBDs adopting the conserved helical sandwich fold previously reported for other ligand-bound nuclear receptors. PPAR-y contains 13 a-helices and four short / -strands, while RXR-a is composed of 11 a-helices and two short yS-strands [3]. This complex is illustrated in Fig. 1.1. 

CURCUMIN ACTIVATES PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-y (PPAR-y)... 

Moreover, studies about lipidogenesis and lipid metabolism have focused on a nuclear receptor, peroxisome proliferation-activated receptor y (PPAR-y). PPAR-y gene is a good example for involvement in a gene-environment interaction. Activation of PPAR-y leads to peroxisome proliferation and increased oxidation of fatty acids. PPAR-y activation results in adipocyte differentiation as well as improved insulin signaling of mature adipocytes. PPAR-y is associated with insulin resistance and blood pressure [5]. In individuals with a specific polymorphism in the PPAR-y (Prol2Ala), a low polyunsaturated-to-saturated fat ratio has been demonstrated to be associated with an increase in body mass index and fasting insulin concentrations [88]. 

It is too early to definitively identify the molecular mechanism(s) by which CLA, or specific isomers thereof, modulate immune reactivity and reduce disease. Peroxisomal proliferator-activated receptor-y (PPAR-y) activation has been proposed as a mechanism by which CLA exerts some of its biological effects (23). Although PPAR-y may play a role in some of the effects caused by dietary CLA, and these effects could be mediated via the downregulation of the NFkB pathway (24), there are some inconsistencies in the isomer-specific effects on the regulation of COX-2 and some of the products of the NFkB pathway. For example, Yu et al. (23) demonstrated that both the t9,cll and the tl0,cl2 isomers of CLA increase PPAR-y, and decrease TNFa however, only the c9,tll isomer decreased endotoxin-induced TNFa (12). If CLA-fed animals are more resistant to endotoxin (above) and if endotoxin downregulates PPAR-y (24), could PPAR-y regulation explain the wide array of effects attributed to dietary CLA ... 

Thiazolidinediones are known to increase insulin sensitivity by stimulating peroxisome proliferator-activated receptor gamma (PPAR-y). Stimulation of PPAR-y results in a number of intracellular and extracellular changes, including an increased number of insulin receptors, increased insulin receptor sensitivity, decreased plasma fatty acid levels, and an increase in a host of intracellular signaling proteins that enhance glucose uptake. 

Murakami, K., Tobe, K., Ide, T., Mochizuki, T., Ohashi, M., Akanuma, Y., Yazaki, Y., and Kadowaki, T. (1998). A novel insulin sensitizer acts as a coligand for peroxisome proliferator-Activated Receptor-Alpha (PPAR-alpha) and PPAR-Gamma Effect of PPAR-Alpha Activation on Abnormal Lipid Metabolism in Liver of Zucker Fatty Rats. Diabetes AT, 1841-1847. 

PCSK9, proprotein convertase subtUisin/kexin type 9 PPAR-y, peroxisome-proliferator-activated receptor-y receptor agonists PPG, post-prandial... 

Numerous agents control mesenchymal stem cell derivation and differentiation of osteoblasts (Fig. 88-2). Adipocytes can be converted to osteoblasts under the control of Runx2 and peroxisome proliferator-activated receptor-y 2 (PPAR y 2). Osteoclasts are derived from the myeloid/monocyte cell line with derivation and differentiation also under the control of numerous agents, some of which are expressed from osteoblasts. ... 

Chia YY, Ton SH, Khalid BAK (2009) Peroxisome proliferator-activaled receptor y (PPARy), lipoprotein lipase (LPL), scaum lipid and HOMA-IR in rats given glycyrrhizic acid. PPAR Res 2010 530265, 6 pp... 

PPAR-y peroxisome proliferator-activated receptor y PRE-M premenopausal... 

A peroxisome proliferator-activated receptor (PPAR) binding site was identified in the murine FATP1 promoter. Several reports have shown a positive regulation of mouse FATPs by ligands that activate PPAR-a, PPAR-y, or PPAR-y/RXR heterodimers. 

NSAID use is also implicated in disease flares in patients with UC. NSAIDs may affect production of both nuclear factor kP and peroxisome proliferator activated receptors (e.g., PPAR-y), both of which are involved in regulating the intestinal responses.11... 

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