Abstract MP39: Metabolic And Gene Expression Profiling Reveal Disparities In Absorption And Metabolism Of Butyrate And Lysine In The Colon Of Spontaneously Hypertensive Rodents Meeting Abstract (Web of Science)

abstract

  • Introduction: Metabolic dysregulation and gut dysbiosis are linked to hypertension. The proximal colon is the main site of metabolism and absorption of short chain fatty acid butyrate. Reduced circulating butyrate concurrently with elevated fecal levels have been reported in human and rodent hypertension. We tested the hypothesis that both the transport and metabolism of butyrate as well as the overall metabolic profile are dysregulated in the colon of the Spontaneously Hypertensive rats (SHR) compared to the Wistar Kyoto (WKY) rats. Methods: Proximal colons from adult male WKY and SHR were placed in oxygenated warmed Ussing chamber buffer containing dextrose, and physiologically relevant concentration of butyrate (40mM) was applied to the luminal side of the colon. Following 1hr incubation, butyrate levels from the luminal and basolateral sides of the Ussing chamber were measured with high performance liquid chromatography to establish butyrate colonic transport and metabolism. Global metabolomics was performed in Ussing chamber media and in the plasma of WKY and SHR to determine the overall metabolic profile. RNA-seq data in the gut epithelium of WKY and SHR was used to elucidate putative signaling pathways altered in rodent hypertension. Results: Both the colonic transport and metabolism of butyrate were significantly impaired in the SHR. In addition, global metabolomics identified reduced levels of essential amino acid L-lysine, among other metabolites, on the basolateral side of the Ussing chamber and in the plasma of the SHR compared to WKY. Enriched metabolite pathways disrupted in the SHR included lysine degradation. RNA-seq revealed differential expression of several fatty acid and amino acid transporters in the colonic epithelium of the SHR. Conclusion: Colonic transport and metabolism of butyrate are reduced in the SHR, accompanied by dysregulation in the metabolism of the essential amino acid lysine in the gut. This, coupled with reduced expression levels of several fatty acid and amino acid transporters in the gut, suggest aberrant host-microbiota communication and colonic metabolic dysfunction in the context of hypertension.

authors

  • Martyniuk, Christopher J
  • Yang, Tao
  • Reznikov, Leah
  • Garrett, Timothy
  • Joe, Bina
  • Zubcevic, Jasenka

publication date

  • 2021

webpage

published in

volume

  • 78

issue

  • Suppl_1