Caveolin‐2 in association with nuclear lamina controls adipocyte hypertrophy. Issue 2 (13th January 2023) - Choi, Moonjeong
Abstract: Here, we identify that Caveolin‐2 (Cav‐2), an integral membrane protein, controls adipocyte hypertrophy in association with nuclear lamina. In the hypertrophy stage of adipogenesis, pY19‐Cav‐2 association with lamin A/C facilitated the disengagement of CCAAT/enhancer‐binding protein α (C/EBPα) and peroxisome proliferator‐activated receptor γ (PPARγ) from lamin A/C and repressed Cav‐2 promoter at the nuclear periphery for epigenetic activation of Cav‐2, and thereby promoted C/EBPα and PPARγ‐induced adipocyte hypertrophy. Stable expression of Cav‐2 was required and retained by phosphorylation, deubiquitination, and association with lamin A/C for the adipocyte hypertrophy. However, obese adipocytes exhibited augmented Cav‐2 stability resulting from the up‐regulation of lamin A/C over lamin B1, protein tyrosine phosphatase 1B (PTP1B), and nuclear deubiquitinating enzyme (DUB), Uchl5. Our findings show a novel epigenetic regulatory mechanism of adipocyte hypertrophy by Cav‐2 at the nuclear periphery.