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ORIGINAL RESEARCH

Identification and Validation of Glycosylation-Related Genes in Obesity and MASH: Insights from Human Liver Samples and a High-Fat Diet Mouse Model

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Pages 363-381 | Received 18 Mar 2024, Accepted 12 Jun 2024, Published online: 05 Jul 2024
 

Abstract

Background

Obesity is reaching epidemic proportions in the developed world. The biosynthesis and degradation of human glycoproteins take place at the highest level in the liver. However, the association between glycosylation and the factors affecting obesity and metabolism-associated steatohepatitis (MASH) is still unclear.

Materials and Methods

Gene expression data of liver samples from obese patients were retrieved from GSE83452 and GSE89632 databases. Difference analysis and machine learning were used to identify hub genes involved in glycosylation and associated with the response of weight loss treatment. A total of 7 glycosylation-related hub genes were identified and then subjected to correlation analysis, immune cells infiltration analysis and ROC (Receiver Operating Characteristic) analysis. We also evaluated the potential function of 7 hub genes in obesity patients. MASH mice were used to validate the glycosylation-related hub genes.

Results

A total of 25 overlapped glycosylation-related genes were identified by DEGs analysis. ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2 were identified as hub genes. Among these hub genes, ACER2, STX17, ARF5, and ENTPD5 were also differential expressed in MASH patients. ENTPD5 showed increased transcription in obese MASH mice.

Conclusion

The current study identified seven glycosylation-related genes, ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2, that might play key roles in the development of obesity. ENTPD5 might play a key role in the development of MASH. These findings provide fresh perspectives for expanding the investigation of obesity and MASH.

Data Sharing Statement

Raw data of this study are available from the corresponding author Xiujun Cai upon request.

Ethics Approval and Consent to Participate

All methods were performed in accordance with the relevant guidelines and regulations. The study is reported in accordance with ARRIVE guidelines, Basel Declaration and the ethical guidelines by the International Council for Laboratory Animal Science (ICLAS). All animal procedures were conducted following the approval of the Zhejiang University Experimental Animal Ethics Committee.

Acknowledgments

Weihua Yu and Jionghuang Chen should be considered as co-first authors. We acknowledge GEO database for providing their platforms and contributors for uploading their meaningful datasets. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This work was supported by Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ24H160021) and Medical Science and Technology Project of Zhejiang Province (Grant Number 2019KY423 and 2021RC069).