Dipeptidyl peptidase IV inhibitors reduce hepatic fibrosis and lipid accumulation in rat intestinal failure-associated liver disease models
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In brief
In brief
This preclinical study demonstrates that DPP4 inhibitors significantly reduce liver fibrosis and fat accumulation in a rat model of intestinal failure-associated liver disease (IFALD). The treatment improved survival rates and decreased fibrosis markers by suppressing TGF-β signaling, offering potential therapeutic insights for managing IFALD in patients dependent on parenteral nutrition.
- DPP4 inhibitors reduced hepatic fibrosis and lipid accumulation in rat models of intestinal failure-associated liver disease (IFALD).
- DPP4-I treatment decreased α-SMA-positive cells and TGF-β levels, suggesting reduced hepatic stellate cell activation and fibrogenesis.
- Survival rate improved with DPP4-I therapy (87.5% vs 70% in controls) in the SBS + TPN model over 21 days.
- DPP4-I may protect against IFALD by inhibiting adipogenesis and suppressing pro-fibrotic TGF-β signaling pathways.
- This preclinical evidence supports investigating DPP4 inhibitors as a potential therapeutic strategy for IFALD in clinical settings.
Written by the GCMD Library team from the article.
Abstract
Purpose
This study aimed to investigate the effectiveness of dipeptidyl peptidase IV inhibitors (DPP4-I) against liver damage, especially fibrosis and lipid accumulation, in a rat intestinal failure-associated liver disease (IFALD) model.
Methods
SD rats were divided into two groups: the Control (n = 7; normal saline + IFALD model) and DPP4-I (n = 7; DPP4-I + IFALD model; short bowel syndrome (SBS) + total parenteral nutrition) groups. All rats were euthanized 21 days postoperatively to obtain tissue samples. Liver fibrosis was evaluated by Sirius Red and α-SMA staining. Liver damage was assessed using the steatosis, activity, and fibrosis score. Inflammation cytokines were examined by ELISA.
Results
The survival rate was comparatively different, being 87.5% in the DPP4-I group and 70.0% in the Control group. Two rats of the Control group showed progressive liver fibrosis in the periportal area with fibrous streaks. Further, the mean area percentage of α-SMA immune-positive cells was significantly lower in the DPP4-I group than in the Control group. TGF-β levels were significantly lower in the DPP4-I group than in the Control group.
Conclusion
DPP4-I administration reduced liver fibrosis in IFALD, possibly by inhibiting DPP4-I-induced adipogenesis and suppressing TGF-β. These results may contribute to elucidating the mechanism of IFALD.