Journal
Scientific Reports
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep38550
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Funding
- National Institutes of Health [R01 AG049772, R21 NS083908, R01 DK099625, I01 BX002408]
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Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a ligand-activated nuclear receptor which controls lipid and glucose metabolism. It is also the master regulator of adipogenesis. In adipocytes, ligand-dependent PPAR gamma activation is associated with proteasomal degradation; therefore, regulation of PPAR gamma degradation may modulate its transcriptional activity. Here, we show that neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ubiquitin ligase, interacts with the hinge and ligand binding domains of PPAR gamma and is a bona fide E3 ligase for PPAR gamma. NEDD4 increases PPAR. stability through the inhibition of its proteasomal degradation. Knockdown of NEDD4 in 3T3-L1 adipocytes reduces PPAR gamma protein levels and suppresses adipocyte conversion. PPAR gamma correlates positively with NEDD4 in obese adipose tissue. Together, these findings support NEDD4 as a novel regulator of adipogenesis by modulating the stability of PPAR gamma.
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