Transient SUMOylation Inhibition In Human Pre-adipocytes Stably Imprints a Transcriptional Beiging Fate

While white and beige adipocytes share a largely similar transcriptome, this identity shift requires significant transcriptional and epigenetic reprogramming. However, the molecular mechanisms governing this transition remain incompletely understood.

Here, we identify SUMOylation as a critical repressor of adipocyte beiging. Using the small-molecule SUMOylation inhibitor TAK-981, we demonstrate that transient SUMOylation inhibition primes human adipocytes to express beiging genes including UCP1 and induce mitochondrial uncoupling in a rosiglitazone-dependent manner. Furthermore, SUMOylation suppresses both the de novo differentiation of human adipose stem cells into beige adipocytes and the transdifferentiation of mature white adipocytes into beige cells.