Association of hepatic DPP-4 and glucagon-like peptide-2 receptor mRNA expression in non-alcoholic fatty liver disease

Abstract

Background: With a global prevalence of about 25%, NAFLD is the most common chronic liver disease in the Western world. Since no drug therapy is yet available to minimize and/or prevent the progression of NAFLD to NASH, researchers are searching for treatment approaches. The association of NAFLD with DPP-4 expression has been demonstrated several times in animal models and in humans at both protein and mRNA levels. Latest studies have unraveled a potential therapeutic effect for DPP-4 inhibitors used in diabetes therapy. The intestinotropic property of GLP-2 showed also a significant improvement in postoperative liver regeneration in mice after partial hepatectomy and is currently been discussed to have also beneficial effects on NAFLD. In this work, we investigated whether hepatic mRNA expression of DPP-4 is associated with pathological findings reflecting liver injury according to NAFLD Activity Score criteria. In addition, we analyzed the association between mRNA expression level of the GLP-2R and histopathological findings in NAFLD. Furthermore, we determined whether there is a correlation between mRNA expressions of DPP-4 with GLP-2R in liver tissue indicating a possible physiologic rescue pathway. Materials and methods: RNA was extracted from FFPE liver tissue of histological specimens of patients who underwent liver resections for different indications, and quantitative RT-PCR was used to measure the mRNA expression level of the DPP-4 and GLP-2R. For quantification, the expression DPP-4 and GLP-2R was normalized to the housekeeping gene H6PDH. Results: In the group comparison, after categorization of the patient collective according to NAS 1-3, steatosis grade, inflammation grade and fibrosis grade, no statistically significant difference in the mRNA expression DPP-4 and GLP-2R could be detected. Spearman’s correlation analysis showed a statistically significant correlation between hepatic mRNA expression of DPP-4 and that of GLP-2R. Conclusion: After stratifying the patient population according to the criteria of the NAFLD activity score into NAS 1-3, steatosis grade 0-3, inflammation grade 1-2 and fibrosis grade 0-4, mRNA expression analysis of DPP-4 and GLP-2R showed no difference between the stages. A correlation of hepatic mRNA expression of DPP-4 and GLP-2R was observed. The underlying causality cannot be explained with the current knowledge.

Date of Award	2022
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Erwin Petek (Supervisor)