Exogenous leptin reinforces intestinal barrier function and protects from colitis

Pharmacol Res. 2019 Sep:147:104356. doi: 10.1016/j.phrs.2019.104356. Epub 2019 Jul 26.

Abstract

Besides its function controlling energy expenditure and food intake, leptin is an important modulator of inflammatory responses. The role of leptin in intestinal inflammation remains controversial, since both pro-inflammatory and anti-inflammatory effects have been reported. This study was carried out to further understand leptin contribution in the inflamed intestinal mucosa. Exogenous PEG-leptin or saline solution was given to C57BL/6 mice for two weeks. After 1 week, acute colitis was induced to C57BL/6 mice using dextran sulfate sodium (DSS) in drinking water. The severity of colitis, inflammatory parameters and mucosal barrier function were evaluated. Overall our results indicate that colitis was less severe in mice receiving leptin, as shown by a decrease in rectal bleeding, epithelial damage and colon inflammatory markers, and improved diarrhea. Leptin-treated mice displayed an increase in the expression of tight junction proteins and proliferative expression markers in colon, indicating a reinforcement in the mucosal barrier function induced by leptin administration. PEG-leptin treatment conferred protection to mice in the DSS model of colitis by reinforcing mucosal barrier function.

Keywords: Barrier function; Experimental colitis; Leptin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / metabolism
  • Colitis / pathology
  • Colitis / prevention & control*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Leptin / administration & dosage*
  • Male
  • Mice, Inbred C57BL
  • Polyethylene Glycols / administration & dosage
  • Protective Agents / administration & dosage*
  • Tight Junctions / metabolism

Substances

  • Leptin
  • Protective Agents
  • Polyethylene Glycols
  • Dextran Sulfate