Dataset Information

USP10 Alleviates Palmitic Acid-induced Steatosis through Autophagy in HepG2 Cells.

ABSTRACT:

Background and aims

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease caused by over-nutrition. Impaired autophagy is closely related to NAFLD progression. Recently, ubiquitin-specific peptidase-10 (USP10) was reported to ameliorate hepatic steatosis, but the underlying mechanism is still unclear. In view of the potential effects of USP10 on autophagy, we investigated whether USP10 alleviated steatosis through autophagy.

Methods

HepG2 cells were treated with palmitic acid (PA) to model NAFLD in vitro. Lentivirus was used to regulate USP10 level in cells. Autophagic regulators were used to autophagic progression in cells. Western blotting, real-time fluorescence quantitative polymerase chain reaction, lipid drop staining and immunofluorescent staining were performed to determine the effect of USP10 on lipid autophagy. Student's t-test and Tukey's post hoc test were used to compare the means among groups.

Results

PA induced cellular steatosis with dependance on autophagy. USP10 overexpression alleviated PA-induced steatosis, restored autophagic activity, promoted autophagic flux, including synthesis and degradation of autophagosomes, and lipid-targeted autophagy. In the presence of autophagy inhibitors, the protective effectiveness of USP10 on steatosis decreased. Furthermore, the specific inhibitor to C-jun N-terminal protein kinase-1 (JNK1), DB07268, abolished USP10-induced autophagy. However, during early stage inhibition of JNK1, compensatory expression of tuberous sclerosis complex-2 (TSC2) maintained autophagy. The degree of TSC2-to-JNK1 compensation was positively associated with USP10 level. Functionally, JNK1 and TSC2 were involved in the lipid-lowering effect of USP10.

Conclusions

USP10 alleviated hepatocellular steatosis in autophagy-dependent manner. JNK1/TSC2 signaling pathways were required for USP10-induced autophagy.

SUBMITTER: Xin SL

PROVIDER: S-EPMC9647103 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

USP10 Alleviates Palmitic Acid-induced Steatosis through Autophagy in HepG2 Cells.

Xin Sheng-Liang SL Pan Xiao-Li XL Xu Xiao-Yuan XY Yu Yan-Yan YY

Journal of clinical and translational hepatology 20220331 1

<h4>Background and aims</h4>Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease caused by over-nutrition. Impaired autophagy is closely related to NAFLD progression. Recently, ubiquitin-specific peptidase-10 (USP10) was reported to ameliorate hepatic steatosis, but the underlying mechanism is still unclear. In view of the potential effects of USP10 on autophagy, we investigated whether USP10 alleviated steatosis through autophagy.<h4>Methods</h4>HepG2 cells were treated wi ...[more]

PMID: 36406315

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Dataset Information

USP10 Alleviates Palmitic Acid-induced Steatosis through Autophagy in HepG2 Cells.

Background and aims

Methods

Results

Conclusions

Publications

USP10 Alleviates Palmitic Acid-induced Steatosis through Autophagy in HepG2 Cells.

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