Page 20 - N. Metabolism and metabolic diseases

[N. Metabolism and metabolic diseases-10]

USP15 promotes non-alcoholic fatty liver disease by

regulation of lipid droplet-associated proteins

Jung-Hwan Baek¹˙²˙#, Myung-Sup Kim¹˙²˙#, Kyung Hee Chun¹˙²˙*

¹Department of Biochemistry & Molecular biology, Yonsei University College of Medicine, Seoul 03722, Korea,

²2Brain Korea 21 PLUS project for Medical Science, , Yonsei University College of Medicine, Seoul 03722, Korea

The Ubiquitin Specific Peptidase 15 (USP15) is a hydrolase that removes conjugated ubiquitin from target proteins.
There have been a number of USP15 studies as to cancer and cancer immunology. However, correlation between

USP15 and metabolic diseases is poorly understood.

In this study, we demonstrate that considerably high expression level of USP15 in liver of steatosis patients. Also,

we confirmed expression level of USP15 is up-regulated in liver tissue of high fat diet fed C57BL/6 wild type mice.
Knock down of USP15 retarded lipid accumulation in hepatocyte. In contrast, overexpression of USP15 increased

lipid accumulation in hepatocyte. We also confirmed that liver tissue specific USP15 KO mice have less hepatic lipid
accumulation than that of USP15 WT. Moreover, we determined that USP15 interacted with lipid droplet-associated

proteins and then up-regulated their protein expressions. Additionally, we identified that up-regulated protein
stability of lipid droplet-associated proteins was due to retardation of ubiquitination by USP15. Taken together, we

proposed that USP15 has positive role of lipid accumulation in hepatocyte and ablation of USP15 expression
prohibits NAFLD.