IGFBP-2 as a biomarker in NAFLD improves hepatic steatosis: an integrated bioinformatics and experimental study.

Abstract

BACKGROUND AND AIMS:

Non-alcoholic fatty liver disease (NAFLD) has become a common chronic liver disease in the world. Simple steatosis (SS) is the early phase of NAFLD. However, the molecular mechanisms underlying the development of steatosis have not yet been fully elucidated.

METHODS:

Two public datasets (GSE48452 and GSE89632) through the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs) in the development of steatosis. A total of 72 participants including 38 normal histological controls and 34 SS patients were included in this study. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analysis were performed to explore the function of DEGs. The results were further confirmed in high-fat diet (HFD)-fed mice and oleate-treated HepG2 cells.

RESULTS:

Total 57 DEGs including 31 up- and 26 down-regulated genes between SS patients and healthy controls were determined. GO and KEGG analysis showed that most of the DEGs were enriched in the ligand-receptor signaling pathways. PPI network construction was used to identify the hub genes of the DEGs. MYC, ANXA2, GDF15, AGTR1, NAMPT, LEPR, IGFBP-2, IL1RN, MMP7, and APLNR were identified as hub genes, and IGFBP-2 expression was found to be reversely associated with hepatic steatosis, fasting insulin, HOMA-IR index, and ALT levels. In HFD-fed mice, hepatic IGFBP-2 was also downregulated and negatively associated with hepatic triglyceride (TG) levels. Moreover, overexpression of IGFBP-2 ameliorated the oleate induced accumulation of TGs in hepatocytes.

CONCLUSIONS:

This study identified novel gene signatures in the hepatic steatosis and will provide new understanding and molecular clues of hepatic steatosis.

• Authors: Xu Chen, Yi Tang, Shen Chen, Wenhua Ling, Qing Wang
• Journal: Endocrine connections (Endocr Connect) Vol. 10 Issue 10 Pg. 1315-1325 (Oct 13 2021) ISSN: 2049-3614 [Print] England
• PMID: 34524971 (Publication Type: Journal Article)