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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

Maternal high-fat diet (HFD) feeding during lactation induces early postnatal hyperalimentation (pHA), early-onset overweight and increased white adipose tissue (WAT) in the murine offspring.(A) Body weight gain (gram) from postnatal day 1 (P1) to P21. Early postnatal hyperalimentation (open square; n = 36 from 9 litters; pHAmouse group), Ctrl (solid square; n = 30 from 6 litters; Ctrl). (B) Body weight (gram) at P70 (Ctrl: n = 21 from 7 litters; pHAmouse: n = 18 from 6 litters). (C) WAT weight (gram) relative to body weight (gram) at P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 11 from 6 litters) and at P70 (Ctrl: n = 11 from 6 litters; pHAmouse: n = 17 from 7 litters). pHAmouse group: white bar, Ctrl: black bar. Mean ± SEM; two way ANOVA test and Bonferroni posttest (A), Mann Whitney test. (B,C); *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.
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f1: Maternal high-fat diet (HFD) feeding during lactation induces early postnatal hyperalimentation (pHA), early-onset overweight and increased white adipose tissue (WAT) in the murine offspring.(A) Body weight gain (gram) from postnatal day 1 (P1) to P21. Early postnatal hyperalimentation (open square; n = 36 from 9 litters; pHAmouse group), Ctrl (solid square; n = 30 from 6 litters; Ctrl). (B) Body weight (gram) at P70 (Ctrl: n = 21 from 7 litters; pHAmouse: n = 18 from 6 litters). (C) WAT weight (gram) relative to body weight (gram) at P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 11 from 6 litters) and at P70 (Ctrl: n = 11 from 6 litters; pHAmouse: n = 17 from 7 litters). pHAmouse group: white bar, Ctrl: black bar. Mean ± SEM; two way ANOVA test and Bonferroni posttest (A), Mann Whitney test. (B,C); *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.

Mentions: To analyze the effect of maternal HFD during lactation on the body weight of the offspring, body weight was determined at P1, P7, P14 and P21 (Fig. 1A). The body weight of the pHAmouse group was greater than in the Ctrl at P21 (p < 0.001) (Fig. 1A), whereas it was unchanged at P70 (Fig. 1B). Furthermore, WAT relative to body weight was greater in the pHAmouse group than in the Ctrl at P21 (p < 0.05) and tended to be higher at P70 (Fig. 1C). In summary, early pHA leads to transient early-onset overweight and obesity at P21; whereas at P70 body weight and WAT is similar to Ctrl.


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)

Maternal high-fat diet (HFD) feeding during lactation induces early postnatal hyperalimentation (pHA), early-onset overweight and increased white adipose tissue (WAT) in the murine offspring.(A) Body weight gain (gram) from postnatal day 1 (P1) to P21. Early postnatal hyperalimentation (open square; n = 36 from 9 litters; pHAmouse group), Ctrl (solid square; n = 30 from 6 litters; Ctrl). (B) Body weight (gram) at P70 (Ctrl: n = 21 from 7 litters; pHAmouse: n = 18 from 6 litters). (C) WAT weight (gram) relative to body weight (gram) at P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 11 from 6 litters) and at P70 (Ctrl: n = 11 from 6 litters; pHAmouse: n = 17 from 7 litters). pHAmouse group: white bar, Ctrl: black bar. Mean ± SEM; two way ANOVA test and Bonferroni posttest (A), Mann Whitney test. (B,C); *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.
© Copyright Policy - open-access
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getmorefigures.php?uid=PMC4834579&req=5

f1: Maternal high-fat diet (HFD) feeding during lactation induces early postnatal hyperalimentation (pHA), early-onset overweight and increased white adipose tissue (WAT) in the murine offspring.(A) Body weight gain (gram) from postnatal day 1 (P1) to P21. Early postnatal hyperalimentation (open square; n = 36 from 9 litters; pHAmouse group), Ctrl (solid square; n = 30 from 6 litters; Ctrl). (B) Body weight (gram) at P70 (Ctrl: n = 21 from 7 litters; pHAmouse: n = 18 from 6 litters). (C) WAT weight (gram) relative to body weight (gram) at P21 (Ctrl: n = 10 from 5 litters; pHAmouse: n = 11 from 6 litters) and at P70 (Ctrl: n = 11 from 6 litters; pHAmouse: n = 17 from 7 litters). pHAmouse group: white bar, Ctrl: black bar. Mean ± SEM; two way ANOVA test and Bonferroni posttest (A), Mann Whitney test. (B,C); *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.
Mentions: To analyze the effect of maternal HFD during lactation on the body weight of the offspring, body weight was determined at P1, P7, P14 and P21 (Fig. 1A). The body weight of the pHAmouse group was greater than in the Ctrl at P21 (p < 0.001) (Fig. 1A), whereas it was unchanged at P70 (Fig. 1B). Furthermore, WAT relative to body weight was greater in the pHAmouse group than in the Ctrl at P21 (p < 0.05) and tended to be higher at P70 (Fig. 1C). In summary, early pHA leads to transient early-onset overweight and obesity at P21; whereas at P70 body weight and WAT is similar to Ctrl.

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