Universität zu Köln

Dinger, Katharina, Kasper, Philipp, Hucklenbruch-Rother, Eva, Vohlen, Christina, Jobst, Eva, Janoschek, Ruth, Bae-Gartz, Inga, van Koningsbruggen-Rietschel, Silke, Plank, Christian, Doetsch, Joerg and Alcazar, Miguel Angel Alejandre (2016). Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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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-1 beta, IL-23, and Tnf-alpha, greater serum leptin and reduced glucose tolerance than Control (Ctrl); (2) less STAT3/AMPK alpha-activation, greater SOCS3 expression and reduced AKT/GSK3 beta-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-alpha. 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dinger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kasper, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Jobst, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoschek, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Bae-Gartz, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED van Koningsbruggen-Rietschel, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED Plank, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel Angel Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-278559
DOI:	10.1038/srep24168
Journal or Publication Title:	Sci Rep
Volume:	6
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AIRWAY SMOOTH-MUSCLE; BODY-MASS INDEX; METABOLIC SYNDROME; LEPTIN RESISTANCE; CHILDHOOD ASTHMA; INFANT GROWTH; INSULIN; CHILDREN; LUNG; PREVALENCE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27855