PPARγ neddylation essential for adipogenesis is a potential target for treating obesity

Abstract

The preadipocyte-to-adipocyte differentiation (adipogenesis) is a key process in fat mass increase and thus it is regarded as a compelling target for preventing or treating obesity. Of adipogenic hormone receptors, peroxisome proliferator-activated receptor gamma (PPARγ) has crucial roles in adipogenesis and lipid accumulation within adipocytes. Here we demonstrate that the NEDD8 (neuronal precursor cell expressed, developmentally downregulated 8)-based post-translation modification (neddylation) of PPARγ is essential for adipogenesis. During adipogenesis, NEDD8 is robustly induced in preadipocytes and conjugates with PPARγ, leading to PPARγ stabilization. When the neddylation process was blocked by NEDD8-targeting siRNAs (or viral vectors) or an inhibitor MLN4924, adipocyte differentiation and fat tissue development were substantially impaired. We also demonstrate that MLN4924 effectively prevents the high-fat diet-induced obesity and glucose intolerance in mice. This study provides a better understanding of how the PPARγ signaling pathway starts and lasts during adipogenesis and a potential anti-obesity strategy that targets the neddylation of PPARγ.

UBC12‐mediated SREBP‐1 neddylation worsens metastatic tumor prognosis

“…Therefore, we speculate that an antagonistic relationship may exist between neddylation and ubiquitination of SREBP‐1 as they compete to bind on the same lysine residue in tumor cells. This idea is in line with another report that neddylated PPARγ is stabilized through the inhibition of ubiquitination at the same domain of PPARγ 35 . Nonetheless, the actual residue involved in SREBP‐1 neddylation remains to be elucidated.…”

Pilot study and bioinformatics analysis of differentially expressed genes in adipose tissues of rats with excess dietary intake

“…The gene network may be associated with PParG, as increased expression of PParG was detected in visceral adipose tissue in our previous study (18). PParG, which is widely described as playing an important role in adipocyte proliferation and differentiation, as well as in the conversion of various cells into adipose-like cells (25)(26)(27)(28)(29)(30), was implicated in the visceral adipose tissue accumulation of the experimental rats in the present study. PParG expression is also potentially associated with serum levels of c-c motif chemokine ligand 2 and interleukin-6 in rats (18), which may facilitate the accumulation of visceral adipose tissue, indicating that PParG serves a role in this phenomenon.…”

Prevalence of hemorrhagic fever with renal syndrome in Qingdao City, China, 2010–2014

“…Suspected HFRS patients were diagnosed according to the criteria in the < Diagnostic criteria for epidemic hemorrhagic fever WS278-2008> issued by the Ministry of Health of China in 200819.…”