Page 21 - N. Metabolism and metabolic diseases

Study on the molecular mechanisms of deubiquitinating enzyme
USP1 in the regulation of adipogenesis

Myung Sup Kim and Kyung-Hee Chun
Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine
BACKGROUND AIM & METHODS

Over-nutrition is currently one of the most costly challenges for In this study, we have focused on adipogenesis mediated by
public health. Although the role of adipocytes in energy storage is ubiquitin specific peptidase 1 (USP1). We treated adipocytes
firmly established, we have only begun to understand the effects with ML323, which is a USP1 specific inhibitor, to investigate
of adipocytes on systemic metabolic homeostasis. Adipocytes are the role of USP1 in adipogenesis in vitro. We also injected
known to sequester excess lipids to prevent toxic lipid ML323 into high fat diet (FHD) fed mice to study the role of
accumulation in tissues such as muscle, liver, and hearth. USP1 in vivo.
RESULTS

Fig 1. USP1 promotes lipid accumulation Fig 2. Inhibition of USP1 by ML323 Fig 3. ML323 reduced lipid accumulation in 3T3-L1 cells.
in 3T3-L1 cells resulted in reduced expression of
adipogenesis related proteins.

Fig 4. Inhibition of USP1 by ML323 Fig 5. Reduced mass of gWAT when Fig 6. Reduced hypertrophic gWAT by inhibition of USP1
resulted in decreased body weight in high injected with ML323 in HFD mice. with ML323.
fat diet mice.

Body weight gWAT
60 *** *** 1.2 *** * 5000
1.0 4000
40
Weight (g) 20 Weight (g) 0.8 Average adipocyte size (μ m 2) 3000 **
0.6
2000
0.4
0.2 1000
0
Control+Vehicle 0.0 0
Control+ML323
HFD+Vehicle Vehicle ML323
HFD+ML323

CONCLUSION REFERENCES

1. USP1 is highly expressed in 1. Nijman, S. M. et al. The deubiquitinating enzyme USP1 regulates the Fanconi anemia
adipocytes and mouse adipose pathway. Mol Cell 17, 331-339, doi:10.1016/j.molcel.2005.01.008 (2005).
tissues. 2. van Twest, S. et al. Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia
Pathway. Mol Cell 65, 247-259, 2016.11.005 (2017).
2. USP1 is involved in adipo-
genesis both in vitro and in vivo. 3. Liang, Q. et al. A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage
responses. Nat Chem Biol 10, 298-304, doi:10.1038/nchembio.1455 (2014).
3. Selective inhibition of USP1
reduces adipogenesis. Contact information Myung Sup Kim, mskim136588@gmail.com