edoc

Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver

AlAsfoor, Shefaa. Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver. 2019, Doctoral Thesis, University of Basel, Faculty of Science.

[img]
Preview
PDF
24Mb

Official URL: http://edoc.unibas.ch/diss/DissB_13084

Downloads: Statistics Overview

Abstract

Macrophages have been recognized as key players in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether pharmacological attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and antidiabetic properties, and how this impact on NAFLD. We analyzed the pro- and anti-inflammatory gene expression of murine macrophages and human monocytes in vitro in the presence or absence of imatinib. In a time-resolved study, we characterized metabolic disease manifestations such as hepatic steatosis, systemic and adipose tissue inflammation as well as lipid and glucose metabolism in obese mice at one and three months of imatinib treatment. Our results showed that imatinib lowered pro-inflammatory markers in murine macrophages and human monocytes in vitro. In obese mice, imatinib reduced TNFα-gene expression in peritoneal and liver macrophages and systemic lipid levels at one month. This was followed by decreased hepatic steatosis, systemic and adipose tissue inflammation and increased insulin sensitivity after three months. As the transcription factor sterol regulatory element-binding protein (SREBP) links lipid metabolism to the innate immune response, we assessed the gene expression of SREBPs and their target genes, which was indeed downregulated in the liver and partially in peritoneal macrophages. In conclusion, targeting both inflammatory and lipogenic pathways in macrophages and liver as shown by imatinib could represent an attractive novel therapeutic strategy for patients with NAFLD.
Advisors:Hess, Christoph and Donath, Marc
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immunobiology (Hess C)
UniBasel Contributors:Hess, Christoph and Donath, Marc
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13084
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (1 Band (verschiedene Seitenzählungen)
Language:English
Identification Number:
Last Modified:08 Jun 2019 04:30
Deposited On:07 Jun 2019 12:35

Repository Staff Only: item control page