title: Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice.
abstract: Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive. Since obesity leads to chronic low-grade inflammation and affects metabolic signaling we hypothesized that postnatal hyperalimentation (pHA) induced by maternal high-fat-diet during lactation leads to early-onset obesity and dysregulates pulmonary adipocytokine/insulin signaling, resulting in metabolic programming of asthma-like disease in adult mice. Offspring with pHA showed at postnatal day 21 (P21): (1) early-onset obesity, greater fat-mass, increased expression of IL-1β, IL-23, and Tnf-α, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPKα-activation, greater SOCS3 expression and reduced AKT/GSK3β-activation in the lung, indicative of leptin resistance and insulin signaling, respectively; (3) increased lung mRNA of IL-6, IL-13, IL-17A and Tnf-α. At P70 body weight, fat-mass, and cytokine mRNA expression were similar in the pHA and Ctrl, but serum leptin and IL-6 were greater, and insulin signaling and glucose tolerance impaired. Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA. Despite unaltered bronchial structure mice after pHA exhibited significantly increased airway reactivity. Our study does not only demonstrate that early-onset obesity transiently activates pulmonary adipocytokine/insulin signaling and induces airway hyperreactivity in mice, but also provides new insights into metabolic programming of childhood obesity-related asthma.
authors.affiliation: Experimental Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Dinger
authors.affiliation: Experimental Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kasper
authors.affiliation: Metabolism and Perinatal Programming, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hucklenbruch-Rother
authors.affiliation: Experimental Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.|Metabolism and Perinatal Programming, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Vohlen
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Jobst
authors.affiliation: Metabolism and Perinatal Programming, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Janoschek
authors.affiliation: Metabolism and Perinatal Programming, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Bae-Gartz
authors.affiliation: Pediatric Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: van Koningsbruggen-Rietschel
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.affiliation: University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Dötsch
authors.affiliation: Experimental Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Alejandre Alcázar
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D059305:Diet, High-Fat; D005260:Female; D007249:Inflammation / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007774:Lactation; D020738:Leptin / Q000097:blood; D008168:Lung / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism
chemical_list: D054392:Adipokines; D024042:Collagen Type I; D007328:Insulin; D007378:Interleukins; D020738:Leptin; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D055372:AMP-Activated Protein Kinases