Press release: SUMOylation inhibition drives an epigenetic "Switch" to reprogram fat cells, sugesting novel strategies to ameliorate metabolism

Patrizia Nothnagel (first author) and Pierre Chymkowitch (senior author)
Patrizia Nothnagel (first author) and Pierre Chymkowitch (senior author)

The group of Dr. Pierre Chymkowitch (Dept. of Microbiology, OUS and IBV, UiO), and their collaborators at NCMBM and IMB, have made a step forward to understanding how fat cells keep their identity and can be reprogrammed. Published in Nucleic Acids Research, the work demonstrates that a brief pharmacological inhibition of SUMOylation using the small molecule TAK-981, when combined with the PPARG agonist rosiglitazone, stably "imprints" a beige differentiation fate in human adipose stem cells. Unlike typical white fat cells that store energy, beige cells can burn fat to generate heat through a process called adaptive thermogenesis or beiging.

Key findings from the study include:

  • Stable Reprogramming: Transient treatment with the SUMOylation inhibitor TAK-981, alongside rosiglitazone, induced stable changes in gene expression and metabolism, leading to the robust induction of canonical beiging markers like UCP1 and increased mitochondrial respiration in mature adipocytes.
  • Epigenetic Mechanism: TAK-981 induces immediate chromatin remodeling and activation of key enhancers, regulatory networks (CEBPA and PPARG), including the loss of repressive chromatin marks (H3K27me3) and gain of activating marks (H3K27ac) at thermogenic gene enhancers.
  • Enhanced Signaling: The mechanism is further enforced by increased cAMP-PKA-p38 signaling and stabilization of beige-promoting transcription activators.
  • Therapeutic Potential: The study suggests that combining SUMOylation inhibition with PPARG activation could increase the body's capacity to burn fat, offering new leads against obesity and related metabolic disorders like type 2 diabetes.
Graphical abstract from the article

 
Links:

Pierre Chymkowitch’s research group:
OUS - Regulation of epigenetic fate by SUMOylation
UiO - Transcriptional Regulation of Cell Fate

Department of Microbiology, OUS

Link to the paper:
Nothnagel PMC, Meslin PA, Wik JA, Dufour D, Strøm YE, Bjørås M, Enserink JM, Skålhegg BS, Briand N, Mathelier A, Chymkowitch P (2026)
Transient SUMOylation Inhibition in Human Pre-Adipocytes Stably Imprints a Transcriptional Beiging Fate
Nucleic Acids Res, 54 (6)
DOI 10.1093/nar/gkag232, PubMed 41854078

 
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