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Tytuł:
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Sleeve gastrectomy improves lipid dysmetabolism by downregulating the USP20-HSPA2 axis in diet-induced obese mice.
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Autorzy:
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Zhang W; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.; Cheeloo College of Medicine, Shandong University, Jinan, China.
Shi B; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.; Cheeloo College of Medicine, Shandong University, Jinan, China.
Li S; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.; Cheeloo College of Medicine, Shandong University, Jinan, China.
Liu Z; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.; Cheeloo College of Medicine, Shandong University, Jinan, China.
Li S; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.; Cheeloo College of Medicine, Shandong University, Jinan, China.
Dong S; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.; Cheeloo College of Medicine, Shandong University, Jinan, China.
Cheng Y; Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
Zhu J; Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
Zhang G; Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
Zhong M; Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.; Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
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Źródło:
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Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2022 Dec 27; Vol. 13, pp. 1041027. Date of Electronic Publication: 2022 Dec 27 (Print Publication: 2022).
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: [Lausanne : Frontiers Research Foundation]
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MeSH Terms:
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Diet, High-Fat*
Obesity*/surgery
Obesity*/complications
Ubiquitin Thiolesterase*
HSP70 Heat-Shock Proteins*
Animals ; Mice ; Gastrectomy/methods ; Lipids ; Mice, Obese
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References:
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Contributed Indexing:
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Keywords: HSPA2; USP20; diet-induced obese; lipid dysmetabolism; sleeve gastrectomy
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Substance Nomenclature:
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0 (Lipids)
EC 3.4.19.12 (Ubiquitin Thiolesterase)
EC 3.4.19.12 (Usp20 protein, mouse)
0 (Hspa2 protein, mouse)
0 (HSP70 Heat-Shock Proteins)
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Entry Date(s):
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Date Created: 20230113 Date Completed: 20230117 Latest Revision: 20230126
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Update Code:
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20240105
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PubMed Central ID:
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PMC9831654
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DOI:
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10.3389/fendo.2022.1041027
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PMID:
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36636478
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Introduction: Obesity is a metabolic disease accompanied by abnormalities in lipid metabolism that can cause hyperlipidemia, non-alcoholic fatty liver disease, and artery atherosclerosis. Sleeve gastrectomy (SG) is a type of bariatric surgery that can effectively treat obesity and improve lipid metabolism. However, its specific underlying mechanism remains elusive.
Methods: We performed SG, and sham surgery on two groups of diet-induced obese mice. Histology and lipid analysis were used to evaluate operation effect. Immunohistochemistry, immunoblotting, real-time quantitative PCR, immunoprecipitation, immunofluorescence and mass spectrometry were used to reveal the potential mechanisms of SG.
Results: Compared to the sham group, the SG group displayed a downregulation of deubiquitinase ubiquitin-specific peptidase 20 (USP20). Moreover, USP20 could promote lipid accumulation in vitro . Co-immunoprecipitation and mass spectrometry analyses showed that heat-shock protein family A member 2 (HSPA2) potentially acts as a substrate of USP20. HSPA2 was also downregulated in the SG group and could promote lipid accumulation in vitro . Further research showed that USP20 targeted and stabilized HSPA2 via the ubiquitin-proteasome pathway.
Conclusion: The downregulation of the USP20-HSPA2 axis in diet-induced obese mice following SG improved lipid dysmetabolism, indicating that USP20-HSPA2 axis was a noninvasive therapeutic target to be investigated in the future.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Zhang, Shi, Li, Liu, Li, Dong, Cheng, Zhu, Zhang and Zhong.)