title: Wound healing in mice with high-fat diet- or ob gene-induced diabetes-obesity syndromes: a comparative study.
abstract: In the past, the genetically diabetic-obese diabetes/diabetes (db/db) and obese/obese (ob/ob) mouse strains were used to investigate mechanisms of diabetes-impaired wound healing. Here we determined patterns of skin repair in genetically normal C57Bl/6J mice that were fed using a high fat diet (HFD) to induce a diabetes-obesity syndrome. Wound closure was markedly delayed in HFD-fed mice compared to mice which had received a standard chow diet (CD). Impaired wound tissue of HFD mice showed a marked prolongation of wound inflammation. Expression of vascular endothelial growth factor (VEGF) was delayed and associated with the disturbed formation of wound margin epithelia and an impaired angiogenesis in the reduced granulation tissue. Normal wound contraction was retarded and disordered. Wound disorders in obese C57Bl/6J mice were paralleled by a prominent degradation of the inhibitor of NFκB (IκB-α) in the absence of an Akt activation. By contrast to impaired wound conditions in ob/ob mice, late wounds of HFD mice did not develop a chronic inflammatory state and were epithelialized after 11 days of repair. Thus, only genetically obese and diabetic ob/ob mice finally developed chronic wounds and therefore represent a better suited experimental model to investigate diabetes-induced wound healing disorders.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Seitz
authors.forename: Christoph
authors.initials: C
authors.lastname: Schürmann
authors.forename: Nadine
authors.initials: N
authors.lastname: Hermes
authors.forename: Elke
authors.initials: E
authors.lastname: Müller
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
authors.forename: Stefan
authors.initials: S
authors.lastname: Frank
authors.forename: Itamar
authors.initials: I
authors.lastname: Goren
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000032:analysis; D020738:Leptin / Q000235:genetics*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D058628:Myofibroblasts / Q000166:cytology; D018919:Neovascularization, Physiologic; D009504:Neutrophils / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D015398:Signal Transduction; D014945:Wound Healing
chemical_list: D004041:Dietary Fats; D053583:Interleukin-1beta; D020738:Leptin