Wt1 facilitates visceral beige fat formation to combat abdominal obesity

Visceral fat has weaker beige adipogenesis than subcutaneous fat with unclear mechanisms. The Wilms tumour gene (Wt1), a visceral adipocyte marker, is highly expressed in visceral adipose tissue (VAT) and visceral adipose-derived stem cells (vADSCs). In our present study, we found its protein levels in VAT decreased under high-fat diet or dexamethasone treatment, but rised in cold exposure or β3-adrenergic receptor agonist treatment, and positively correlate with uncoupling protein-1 (UCP1). Wt1 knockdown in vADSCs elevated PR domain containing 16 (PRDM16) and UCP1 mRNA but reduced their protein levels, alongside decreased ubiquitin-conjugating enzyme 9 (UBC9). Knockdown of UBC9 did not affect the mRNA levels of Wt1, PRDM16 or UCP1, but significantly reduced PRDM16 and UCP1 protein levels. Glucocorticoids including hydrocortisone, methylprednisolone and dexamethasone (Dex) dose-dependently suppress Wt1, UCP1, Alpha-enolase (ENO1) and Pyruvate kinase muscle isozyme M2 (PKM2) levels, which could be reversed by Wt1 overexpression. These findings explore the effects of Wt1 on beige remodelling of visceral adipose which might be related to the up-regulation of UBC9, and provide clues for treating abdominal obesity caused either by HFD or by glucocorticoids in a non-sympathetic-dependent manner.