Experimental analysis of risk factors for ulcerative dermatitis in mice

Exp Dermatol. 2012 Sep;21(9):712-3. doi: 10.1111/j.1600-0625.2012.01558.x.

Abstract

Ulcerative dermatitis (UD) is a severe inflammatory skin disorder with an unknown aetiology. Recently, insulin receptor substrate 1 KO mice were shown to be fully resistant to UD. In this study, we showed that high-fat diet (HFD) feeding significantly increased incidence of UD in wild type (WT) C57BL/6 mice, as did lithium-mediated inhibition of GSK3-β, which is a key negative regulator of IRS1. In contrast to WT mice, resistance to UD was fully preserved in HFD-fed Irs1-KO mice. Our results identify IRS1 as a key determinant of UD pathogenesis and establish a direct link between diet composition, obesity-induced inflammation and chronic ulceration.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dermatitis / complications
  • Dermatitis / etiology*
  • Dermatitis / metabolism
  • Dietary Fats / administration & dosage*
  • Dietary Fats / adverse effects
  • Glycogen Synthase Kinase 3 / drug effects
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism*
  • Lithium / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Risk Factors
  • Signal Transduction
  • Skin Ulcer / complications
  • Skin Ulcer / etiology*
  • Skin Ulcer / metabolism

Substances

  • Dietary Fats
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Lithium
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3