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Kidney Week

Abstract: TH-PO0813

Fiber-Based Diets and Region-Specific Intestinal Expression of GLP-1 Receptor in a Rat Model of CKD

Session Information

Category: Cardiovascular-Kidney-Metabolic Health

  • 601 Cardiovascular-Kidney-Metabolic Health: Basic

Authors

  • Al-Khattab, Shakoora, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Biruete, Annabel, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • O'Neill, Kalisha, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Srinivasan, Shruthi, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Glucagon-like peptide-1 (GLP-1) agonists have reshaped the therapeutic landscape of kidney and metabolic diseases. However, far less is known about its cognate receptor, GLP-1R. We have shown that dietary fiber impacts downstream complications of chronic kidney disease (CKD), though its impact on GLP-1 signaling pathways remains poorly understood. Here we investigate the impact of fiber-based diets on GLP-1R expression in the small intestine using a rat-model of CKD. We postulate that dietary fibers modulate GLP-1R expression in a tissue-specific manner that in turn regulates the effect of GLP-1. This work is vital to understanding how dietary fibers and GLP-1R signaling impact CKD-associated metabolic dysregulation.

Methods

Male Cy/+ rats, a slowly progressive model of CKD, were fed 10% inulin (fermentable fiber), psyllium (viscous fiber), pectin (fermentable and viscous fiber), or cellulose (control) diets for 10 weeks duration until 32 weeks of age (stage 4/5 CKD). Segmental intestinal tissues were harvested, and total RNA was isolated. GLP-1R expression was quantified using RT/PCR.

Results

Dietary fibers including inulin, psyllium, and pectin decrease GLP-1R expression in duodenum from CKD rats. In contrast, inulin increased GLP-1R expression within the ileum whereas psyllium and pectin had no significant effect. CKD rats also exhibited significantly lower expression of GLP-1R in the ileum when compared to controls. No significant difference was found in GLP-1R expression in the duodenum between CKD and normal controls.

Conclusion

CKD suppresses the expression of GLP-1R within ileum when compared to normal rats. This expression is restored by an inulin-based diet. All three dietary fibers significantly modulated the expression of GLP-1R within the duodenum. This study highlights the dynamic nature of GLP-1R expression that is highly sensitive to dietary intervention and suggest dietary interventions play a vital role in modulating receptor availability throughout the small intestine. Further research is needed to understand how this in turn impacts clinical efficacy of GLP-1-based therapies in CKD.