Distinct functions of PPARγ isoforms in regulating adipocyte plasticity.

A better understanding of the mechanisms underlying obesity and its comorbidities is key to designing new therapies and treatments. PPARγ is a master regulator of adipocyte biology but the functions of its isoforms are poorly distinguished. Here we demonstrated that PPARγ1 is preferentially expressed in catabolic fat depots while PPARγ2 presents itself at a higher level in browning-resistant depots. PPARγ2, but not PPARγ1, responds to endogenous ligands to induce adipogenesis, and the isoforms regulate distinct sets of white and brown adipocyte genes. Moreover, PPARγ1 negatively correlates while PPARγ2 positively correlates with adiposity in human subcutaneous and visceral fat. These results together indicate that PPARγ1 and PPARγ2 have distinct functions in regulating adipocyte plasticity, and future research should take into account the binary roles of both isoforms in order to identify druggable gene targets and pathways relevant for treatment of metabolic disorders.

Identification, organ expression and ligand-dependent expression levels of peroxisome proliferator activated receptors in grass carp (Ctenopharyngodon idella).

The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor family, and can regulate various genes involved in lipid metabolism. The aim of the present study was to investigate the tissue distribution patterns of PPARs and their ligand specificities in grass carp. We cloned three PPAR isotypes of the species and evaluated their organ distribution patterns using real-time PCR. Through analyzing the deduced amino acid sequences identities between the products cloned in grass carp and those described in other species, we concluded that the same type of PPAR amino acid sequences in different species were with high homology, and different subtypes of PPAR in the same species were with low homology. The mRNA constitutive expression level of PPARα predominated in the liver, but was weak in other tested tissues. PPARß was present in all tested organs, and particularly abundant in heart, liver and muscle. PPARγ was only detected in the liver, and to a lesser extent in brain, muscle and visceral adipose tissue. Grass carp were intraperitoneally injected with 50 mg kg(-1) body mass (bw) dose of clofibrate, 42 mg kg(-1) bw dose of 2-bromo palmitate and 1 mg kg(-1) bw dose of 15-deoxy-Δ(12,14) prostaglandin J2 (15d-PGJ2), respectively, and the relative changes of the mRNA abundance of PPARs in liver were analyzed by real-time PCR. Clofibrate was able to increase the expressions of both PPARα and ß, but was not able to for PPARγ. 2-bromo palmitate could affect the expressions of both PPARß and γ, but was not able to for PPARα. 15d-PGJ2 was able to induce PPARß expression, but PPARα and γ were not enhanced. Consequently, these results indicate that clofibrate, 2-bromo palmitate and 15d-PGJ2 could be applied as the activators of grass carp PPARs.

The PPARgamma coding region and its role in visceral obesity.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand activated transcription factor, plays many essential roles of biological function in higher organisms. The PPARgamma is mainly expressed in adipose tissue. It regulates the transcriptional activity of genes by binding with other transcription factor. The PPARgamma coding region has been found to be closest to that of monkey in ours and other research groups. Thus, monkey is a more suitable animal model for future PPARgamma studying, although mice and rat are frequently being used. The PPARgamma is involved in regulating alterations of adipose tissue masses result from changes in mature adipocyte size and/or number through a complex interplay process called adipogenesis. However, the role of PPARgamma in negatively regulating the process of adipogenesis remains unclear. This review may help we investigate the differential expression of key transcription factor in adipose tissue in response to visceral obesity-induced diet in vivo. The study may also provide valuable information to define a more appropriate physiological condition in adipogenesis which may help to prevent diseases cause by negative regulation of the transcription factors in adipose tissue.