Targeted microRNA profiling reveals that exendin-4 modulates the expression of several microRNAs to reduce steatosis in HepG2 cells
| dc.contributor.author | Khalifa, Olfa | |
| dc.contributor.author | Ouararhni, Khalid | |
| dc.contributor.author | Errafii, Khaoula | |
| dc.contributor.author | Alajez, Nehad M. | |
| dc.contributor.author | Arredouani, Abdelilah | |
| dc.date.accessioned | 2025-09-30T06:37:44Z | |
| dc.date.available | 2025-09-30T06:37:44Z | |
| dc.date.issued | 2023-07-18 | |
| dc.description | Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic illness defined by excessive fat accumulation in the liver due to causes other than excessive alcohol use or viral infection. This illness encompasses simple steatosis (benign fatty infiltration), non-alcoholic steatohepatitis (NASH) (fatty infiltration with inflammation), fibrosis, and cirrhosis, which can develop into hepatocellular cancer [1,2,3]. NAFLD is linked to insulin resistance and genetic vulnerability [4], and because of the rising incidence of obesity and obesity-related metabolic syndrome, NAFLD has become the primary cause of chronic liver disease in industrialized nations and the third cause of liver transplantation [5,6,7,8]. Therefore, NAFLD is a significant public health issue [9] but presently has no approved pharmacotherapy. Sustained weight loss of at least 5% of the total body weight is beneficial for NAFLD patients, as reflected by improved liver enzyme levels and reduced liver fat content [10,11,12]. A loss of more than 10% of body weight appears to minimize inflammation and harm to liver cells and may even repair some fibrosis damage [13,14,15]. Nevertheless, most people find it challenging to achieve the weight loss required to improve their NAFLD and much harder to maintain their weight loss. | |
| dc.description.abstract | Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aim to investigate how the GLP-1RA exendin-4 (Ex-4) affects the microRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from control, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment pathway analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, insulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigation. Keywords: Steatosis, NAFLD, exendin-4, miRNAs, HepG2, GLP-1R agonist | |
| dc.identifier.citation | Khalifa, O., Ouararhni, K., Errafii, K., Alajez, N. M., & Arredouani, A. (2023). Targeted microRNA profiling reveals that exendin-4 modulates the expression of several microRNAs to reduce steatosis in HepG2 cells. International Journal of Molecular Sciences, 24(14), 11606. | |
| dc.identifier.doi | https://doi.org/10.3390/ijms241411606 | |
| dc.identifier.uri | https://repository.adu.ac.ae/handle/1/7532 | |
| dc.language.iso | en | |
| dc.publisher | MDPI | |
| dc.title | Targeted microRNA profiling reveals that exendin-4 modulates the expression of several microRNAs to reduce steatosis in HepG2 cells | |
| dc.type | Article |