title: Hematopoietic Kit Deficiency, rather than Lack of Mast Cells, Protects Mice from Obesity and Insulin Resistance.
abstract: Obesity, insulin resistance, and related pathologies are associated with immune-mediated chronic inflammation. Kit mutant mice are protected from diet-induced obesity and associated co-morbidities, and this phenotype has previously been attributed to their lack of mast cells. We performed a comprehensive metabolic analysis of Kit-dependent Kit(W/Wv) and Kit-independent Cpa3(Cre/+) mast-cell-deficient mouse strains, employing diet-induced or genetic (Lep(Ob/Ob) background) models of obesity. Our results show that mast cell deficiency, in the absence of Kit mutations, plays no role in the regulation of weight gain or insulin resistance. Moreover, we provide evidence that the metabolic phenotype observed in Kit mutant mice, while independent of mast cells, is immune regulated. Our data underscore the value of definitive mast cell deficiency models to conclusively test the involvement of this enigmatic cell in immune-mediated pathologies and identify Kit as a key hematopoietic factor in the pathogenesis of metabolic syndrome.
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, D-69120, Germany.
authors.forename: Dario A
authors.initials: DA
authors.lastname: Gutierrez
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, D-69120, Germany.
authors.forename: Sathya
authors.initials: S
authors.lastname: Muralidhar
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, D-69120, Germany.
authors.forename: Thorsten B
authors.initials: TB
authors.lastname: Feyerabend
authors.affiliation: Institute for Diabetes and Cancer IDC, Helmholtz Center Munich, and Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Herzig
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, D-69120, Germany. Electronic address: hr.rodewald@dkfz.de.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
mesh_terms: D000818:Animals; D017353:Gene Deletion; D006410:Hematopoiesis; D007333:Insulin Resistance; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D024821:Metabolic Syndrome / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019089:Stem Cell Factor / Q000235:genetics* / Q000276:immunology; D059467:Transcriptome
chemical_list: D019089:Stem Cell Factor