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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

Early-onset overweight with early-onset obesity induces glucose intolerance and mild hyperinsulinemia.(A,B) Intraperitoneal glucose tolerance test (i.p. GTT) at postnatal day 21 (A) and 70 (B) (P21 and P70); blood glucose levels (mg/dl) 0, 15, 30, 60, and 120 min after i.p. injection of glucose. P21: Ctrl, n = 12 from 5 litters; pHAmouse: n = 6 from 6 litters: P70: Ctrl: n = 7 from 3 litters; pHAmouse: n = 16 from 5 litters. two way ANOVA test and Bonferroni posttest. Early postnatal hyperalimentation (open square; pHAmousegroup), Ctrl (solid square; Ctrl). (C,D) Serum levels of insulin (ng/ml) at P21 (C): Ctrl: n = 7 from 5 litters; pHAmouse: n = 7 from 6 litters, and P70 (D): Ctrl: n = 5 from 4 litters; pHAmouse, n = 6 from 3 litters. Mann Whitney test; *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.
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f5: Early-onset overweight with early-onset obesity induces glucose intolerance and mild hyperinsulinemia.(A,B) Intraperitoneal glucose tolerance test (i.p. GTT) at postnatal day 21 (A) and 70 (B) (P21 and P70); blood glucose levels (mg/dl) 0, 15, 30, 60, and 120 min after i.p. injection of glucose. P21: Ctrl, n = 12 from 5 litters; pHAmouse: n = 6 from 6 litters: P70: Ctrl: n = 7 from 3 litters; pHAmouse: n = 16 from 5 litters. two way ANOVA test and Bonferroni posttest. Early postnatal hyperalimentation (open square; pHAmousegroup), Ctrl (solid square; Ctrl). (C,D) Serum levels of insulin (ng/ml) at P21 (C): Ctrl: n = 7 from 5 litters; pHAmouse: n = 7 from 6 litters, and P70 (D): Ctrl: n = 5 from 4 litters; pHAmouse, n = 6 from 3 litters. Mann Whitney test; *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.

Mentions: To clarify whether the increase of adipocytokines is related to impaired glucose metabolism we tested glucose tolerance by assessing intraperitoneal glucose tolerance test (i.p. GTT). At P21, pHAmouse showed significantly greater serum glucose levels compared to Ctrl at 15 min (p < 0.001) and 30 min (p < 0.05) following i.p. glucose injection (Fig. 5A). At P70, glucose tolerance was partially restored compared to P21, but serum glucose was still higher at 15 min (p < 0.01) and 60 min (p < 0.001) in the pHAmouse group when compared to the Ctrl (Fig. 5B). Insulin in serum was greater in the pHAmouse group than in the Ctrl at P21 (p = 0.073 by Mann Whitney test; Fig. 5C), but not at P70 (Fig. 5D).


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)

Early-onset overweight with early-onset obesity induces glucose intolerance and mild hyperinsulinemia.(A,B) Intraperitoneal glucose tolerance test (i.p. GTT) at postnatal day 21 (A) and 70 (B) (P21 and P70); blood glucose levels (mg/dl) 0, 15, 30, 60, and 120 min after i.p. injection of glucose. P21: Ctrl, n = 12 from 5 litters; pHAmouse: n = 6 from 6 litters: P70: Ctrl: n = 7 from 3 litters; pHAmouse: n = 16 from 5 litters. two way ANOVA test and Bonferroni posttest. Early postnatal hyperalimentation (open square; pHAmousegroup), Ctrl (solid square; Ctrl). (C,D) Serum levels of insulin (ng/ml) at P21 (C): Ctrl: n = 7 from 5 litters; pHAmouse: n = 7 from 6 litters, and P70 (D): Ctrl: n = 5 from 4 litters; pHAmouse, n = 6 from 3 litters. Mann Whitney test; *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4834579&req=5

f5: Early-onset overweight with early-onset obesity induces glucose intolerance and mild hyperinsulinemia.(A,B) Intraperitoneal glucose tolerance test (i.p. GTT) at postnatal day 21 (A) and 70 (B) (P21 and P70); blood glucose levels (mg/dl) 0, 15, 30, 60, and 120 min after i.p. injection of glucose. P21: Ctrl, n = 12 from 5 litters; pHAmouse: n = 6 from 6 litters: P70: Ctrl: n = 7 from 3 litters; pHAmouse: n = 16 from 5 litters. two way ANOVA test and Bonferroni posttest. Early postnatal hyperalimentation (open square; pHAmousegroup), Ctrl (solid square; Ctrl). (C,D) Serum levels of insulin (ng/ml) at P21 (C): Ctrl: n = 7 from 5 litters; pHAmouse: n = 7 from 6 litters, and P70 (D): Ctrl: n = 5 from 4 litters; pHAmouse, n = 6 from 3 litters. Mann Whitney test; *p < 0.05, **p < 0.01, ***p < 0.001; n.s. = not significant.
Mentions: To clarify whether the increase of adipocytokines is related to impaired glucose metabolism we tested glucose tolerance by assessing intraperitoneal glucose tolerance test (i.p. GTT). At P21, pHAmouse showed significantly greater serum glucose levels compared to Ctrl at 15 min (p < 0.001) and 30 min (p < 0.05) following i.p. glucose injection (Fig. 5A). At P70, glucose tolerance was partially restored compared to P21, but serum glucose was still higher at 15 min (p < 0.01) and 60 min (p < 0.001) in the pHAmouse group when compared to the Ctrl (Fig. 5B). Insulin in serum was greater in the pHAmouse group than in the Ctrl at P21 (p = 0.073 by Mann Whitney test; Fig. 5C), but not at P70 (Fig. 5D).

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