title: A humanized osteopontin mouse model and its application in immunometabolic obesity studies.
abstract: Osteopontin (OPN) is a multifunctional protein involved in several inflammatory processes and pathogeneses including obesity-related disorders and cancer. OPN binds to a variety of integrin receptors and CD44 resulting in a proinflammatory stimulus. Therefore, OPN constitutes a novel interesting target to develop new therapeutic strategies, which counteract OPN's proinflammatory properties. We established a humanized SPP1 (hSPP1) mouse model and evaluated its suitability as a model for obesity and insulin resistance. Unchallenged hSPP1 animals did not significantly differ in body weight and gross behavioral properties compared to wild-type (WT) animals. High-fat diet-challenged hSPP1 similarly developed obesity and inflammation, whereas insulin resistance was markedly changed. However, OPN expression profile in tissues was significantly altered in hSPP1 compared to WT depending on the diet. In conclusion, we developed a versatile humanized model to study the action of OPN in vivo and to develop strategies that target human OPN in a variety of pathologies.
authors.affiliation: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Grün
authors.affiliation: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria; FH Campus Wien, University of Applied Sciences, Department Health, Section Biomedical Science, Vienna, Austria.
authors.forename: Karina
authors.initials: K
authors.lastname: Zeyda
authors.affiliation: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Veronica
authors.initials: V
authors.lastname: Moreno-Viedma
authors.affiliation: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Strohmeier
authors.affiliation: AFFiRiS AG, Vienna, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Staffler
authors.affiliation: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria; Department of Pediatrics and Adolescent Medicine, Clinical Division of Pediatric Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Vienna Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.affiliation: Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy and Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: thomas.stulnig@meduniwien.ac.at.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005838:Genotype; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D006984:Hypertrophy; D007249:Inflammation / Q000473:pathology; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D053495:Osteopontin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D053495:Osteopontin