Ghrelin upregulates PepT1 activity in the small intestine epithelium of rats with sepsis

Biomed Pharmacother. 2017 Feb;86:669-676. doi: 10.1016/j.biopha.2016.12.026. Epub 2016 Dec 27.

Abstract

Background: Sepsis causes nutritional substrate malabsorption; hence, preventing gut barrier problems and improving the nutritional status in sepsis is a compelling issue.

Aims: We tested whether ghrelin administration affects peptide transporter 1 (PepT1) activity in the intestinal epithelium of rats with sepsis.

Methods: Sixty male Sprague-Dawley rats were randomly divided into sham-operated, sepsis, and ghrelin-treated groups. The cecum of sham-operated rats was separated after laparotomy without ligation and perforation. Sepsis group rats underwent cecal ligation and puncture (CLP). Mucosal specimens were used for immunohistochemstry, real-time PCR, and western blotting to detect PepT1 distribution, and mRNA and protein expression levels, respectively. TNF-α, IL-1β, and ghrelin levels were estimated in serum and intestinal mucosal tissue by ELISA. High-performance liquid chromatography was used to measure PepT1 uptake by the epithelial cells. Moreover, survival, body weight, and food intake of the rats were recorded during the 7-day treatment period.

Results: All rats in the sham-operated group survived, and 80% of rats in the sepsis group died within 7d of CLP. Treatment with ghrelin attenuated the CLP-induced body weight loss, intestine mucosa damage, and the survival rate was better. In addition, ghrelin attenuated increases in TNF-α and IL-1β production. The expressions of PepT1 mRNA and protein were higher in ghrelin-treated group rats than in sepsis rats. Moreover, the uptake function of PepT1 was better in ghrelin-treated group rats.

Conclusion: Ghrelin treatment can reduce the inflammatory response and greatly upregulate the physiological function of PepT1 in intestinal epithelial cells of rats with sepsis.

Keywords: Cecal ligation and puncture; Ghrelin; Inflammatory response; PepT1; Sepsis.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Ghrelin / metabolism*
  • Interleukin-1beta / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / metabolism*
  • Ligation / methods
  • Male
  • Peptide Transporter 1
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / metabolism*
  • Symporters / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / physiology*

Substances

  • Ghrelin
  • Interleukin-1beta
  • Peptide Transporter 1
  • RNA, Messenger
  • Slc15a1 protein, rat
  • Symporters
  • Tumor Necrosis Factor-alpha