Experimental analysis of risk factors for ulcerative dermatitis in mice.
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.
Max Planck Institute for Biology of Ageing, Cologne, Germany.
Brit
B
Neuhaus
Carien M
CM
Niessen
Andrea
A
Mesaros
Dominic J
DJ
Withers
Thomas
T
Krieg
Linda
L
Partridge
D000818:Animals; D003872:Dermatitis / Q000150:complications / Q000209:etiology* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012307:Risk Factors; D015398:Signal Transduction; D012883:Skin Ulcer / Q000150:complications / Q000209:etiology* / Q000378:metabolism
D004041:Dietary Fats; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3