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Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice.

Dinger K, Kasper P, Hucklenbruch-Rother E, Vohlen C, Jobst E, Janoschek R, Bae-Gartz I, van Koningsbruggen-Rietschel S, Plank C, Dötsch J, Alejandre Alcázar MA - Sci Rep (2016)

Bottom Line: Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive.Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA.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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Greater expression of pro-asthmatic cytokines (IL-4, IL-6, IL-13, IL-17A, and TNFα) in lungs of mice with early postnatal hyperalimentation (pHA) and early-onset obesity.(A,B) Total lung mRNA expression of genes encoding Il-4, Il-6, Il-13, Il-17A and Tnf-α was assessed by quantitative real-time PCR at (A) P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 10 from 6 litters) and at (B) P70 (Ctrl: n = 9–10 from 6 litters; pHAmouse: n = 10 from 6 litters). The Ctrl was normalized to 1; early postnatal hyperalimentation (white bar; pHAmousegroup). Mean ± SEM; Mann Whitney test; *p < 0.05, **p < 0.01; n.s. = not significant.
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f3: Greater expression of pro-asthmatic cytokines (IL-4, IL-6, IL-13, IL-17A, and TNFα) in lungs of mice with early postnatal hyperalimentation (pHA) and early-onset obesity.(A,B) Total lung mRNA expression of genes encoding Il-4, Il-6, Il-13, Il-17A and Tnf-α was assessed by quantitative real-time PCR at (A) P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 10 from 6 litters) and at (B) P70 (Ctrl: n = 9–10 from 6 litters; pHAmouse: n = 10 from 6 litters). The Ctrl was normalized to 1; early postnatal hyperalimentation (white bar; pHAmousegroup). Mean ± SEM; Mann Whitney test; *p < 0.05, **p < 0.01; n.s. = not significant.

Mentions: We measured pulmonary mRNA of Il-1β, Il-4, Il-6, Il-13, Il-17A, Il-23 and TNF-α at postnatal day 21 (P21) and P70, and found a significant greater expression of Il-6 (p < 0.05), Il-13 (p < 0.05), Il-17A (p < 0.01) and Tnf-α (p < 0.01), but not of Il-1β and Il-23 (data not shown) in pHAmouse at P21 than in Ctrl (Fig. 3A); whereas at P70, no significant differences were detectable (Fig. 3B).


Early-onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma-like disease in mice.

Dinger K, Kasper P, Hucklenbruch-Rother E, Vohlen C, Jobst E, Janoschek R, Bae-Gartz I, van Koningsbruggen-Rietschel S, Plank C, Dötsch J, Alejandre Alcázar MA - Sci Rep (2016)

Greater expression of pro-asthmatic cytokines (IL-4, IL-6, IL-13, IL-17A, and TNFα) in lungs of mice with early postnatal hyperalimentation (pHA) and early-onset obesity.(A,B) Total lung mRNA expression of genes encoding Il-4, Il-6, Il-13, Il-17A and Tnf-α was assessed by quantitative real-time PCR at (A) P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 10 from 6 litters) and at (B) P70 (Ctrl: n = 9–10 from 6 litters; pHAmouse: n = 10 from 6 litters). The Ctrl was normalized to 1; early postnatal hyperalimentation (white bar; pHAmousegroup). Mean ± SEM; Mann Whitney test; *p < 0.05, **p < 0.01; n.s. = not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834579&req=5

f3: Greater expression of pro-asthmatic cytokines (IL-4, IL-6, IL-13, IL-17A, and TNFα) in lungs of mice with early postnatal hyperalimentation (pHA) and early-onset obesity.(A,B) Total lung mRNA expression of genes encoding Il-4, Il-6, Il-13, Il-17A and Tnf-α was assessed by quantitative real-time PCR at (A) P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 10 from 6 litters) and at (B) P70 (Ctrl: n = 9–10 from 6 litters; pHAmouse: n = 10 from 6 litters). The Ctrl was normalized to 1; early postnatal hyperalimentation (white bar; pHAmousegroup). Mean ± SEM; Mann Whitney test; *p < 0.05, **p < 0.01; n.s. = not significant.
Mentions: We measured pulmonary mRNA of Il-1β, Il-4, Il-6, Il-13, Il-17A, Il-23 and TNF-α at postnatal day 21 (P21) and P70, and found a significant greater expression of Il-6 (p < 0.05), Il-13 (p < 0.05), Il-17A (p < 0.01) and Tnf-α (p < 0.01), but not of Il-1β and Il-23 (data not shown) in pHAmouse at P21 than in Ctrl (Fig. 3A); whereas at P70, no significant differences were detectable (Fig. 3B).

Bottom Line: Childhood obesity is a risk factor for asthma, but the molecular mechanisms linking both remain elusive.Peribronchial elastic fiber content, bronchial smooth muscle layer, and deposition of connective tissue were not different after pHA.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.

View Article: PubMed Central - PubMed

Affiliation: Experimental Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.

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.

No MeSH data available.


Related in: MedlinePlus