Aerobic exercise improves intestinal mucosal barrier dysfunction through TLR4/MyD88/NF-κB signaling pathway in diabetic rats

Biochem Biophys Res Commun. 2022 Dec 17:634:75-82. doi: 10.1016/j.bbrc.2022.09.075. Epub 2022 Sep 22.

Abstract

This study examined the effects of aerobic exercise on the intestinal mucosal barrier dysfunction in diabetic rats. We established a diabetic rats model consisting of three groups: normal control (NC), diabetes control (DC), and diabetes eight-week aerobic exercise (DE). We measured serum fasting blood glucose (FBG), insulin (INS), diamine oxidase (DAO), D(-)-lactate (D-Lac), lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and insulin resistance index (HOMA-IR). Intestinal sections of tissue were stained with H&E and examined using transmission electron microscopy. Expressions of occludin, claudin-1, toll-like receptor-4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), and nuclear factor-κB (NF-κB) in small intestinal mucosa were determined by Western Blot. In comparison to NC, FBG, HOMA-IR, DAO, D-Lac, TNF-α, IL-6, and LPS were increased (P < 0.05) in DC, whereas INS, villus height, crypt depth, and mucosal thickness were decreased (P < 0.05). In comparison to DC, FBG, DAO, D-Lac, TNF-α, and LPS were decreased (P < 0.05) in DE, whereas INS, villus height, crypt depth, and mucosal thickness were increased (P < 0.05). In comparison to NC, occludin and claudin-1 were decreased (P < 0.05) in DC, whereas TLR4, MyD88, and NF-κB were increased (P < 0.05). In comparison to DC, occludin and claudin-1 were increased (P < 0.05) in DE, whereas TLR4, MyD88, and NF-κB were decreased (P < 0.05). In conclusion, eight-week aerobic exercise improved intestinal mucosal barrier dysfunction in diabetic rats, by inhibiting LPS release, TLR4/MyD88/NF-κB signaling pathway, and pro-inflammatory cytokines expression.

Keywords: Claudin-1; Intestinal permeability; LPS; Lipopolysaccharide; Pro-inflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Claudin-1 / metabolism
  • Diabetes Mellitus, Experimental* / therapy
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / metabolism
  • Lipopolysaccharides / pharmacology
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B* / metabolism
  • Occludin / metabolism
  • Rats
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Toll-Like Receptor 4
  • Myeloid Differentiation Factor 88
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Occludin
  • Interleukin-6
  • Claudin-1
  • Tlr4 protein, rat
  • Myd88 protein, rat