Relationship between leptin and lung function in young healthy children

Eising, Jacobien B.; Uiterwaal, Cuno S.P.M.; Evelein, Annemieke M. V.; Visseren, Frank L.J.; Ent, Cornelis K. van der

doi:10.1183/09031936.00149613

Cited by 30 publications

(27 citation statements)

References 13 publications

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“…Maternal obesity might be linked to structural change in the respiratory system by increased secretion of adipokines such as leptin. Leptin receptors are expressed in the lung, leptin regulates fetal lung cell maturation, and leptin levels have been shown to be inversely related to forced expiratory volume in children …”

Section: Discussionmentioning

confidence: 99%

Maternal body mass index: Relation with infant respiratory symptoms and infections

Rajappan

Pearce

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et al. 2017

Pediatric Pulmonology

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Section: Discussionmentioning

confidence: 99%

Maternal body mass index: Relation with infant respiratory symptoms and infections

Rajappan

Pearce

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et al. 2017

Pediatric Pulmonology

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“…Leptin receptors have been identified in the human bronchial and alveolar epithelial cells, bronchial smooth muscle cells and bronchial submucosa. In a recent study we have shown an association between higher leptin plasma concentration and lower lung function (forced expiratory volume in 1 s (FEV1)) in healthy children, which suggests a functional role for this hormone in the respiratory system [10]. Children of mothers with increased fat mass are probably exposed to higher circulating levels of leptin, which may have consequences for development of the respiratory system.…”

Section: Introductionmentioning

confidence: 99%

Maternal body mass index, neonatal lung function and respiratory symptoms in childhood

2015

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Recent studies have shown that maternal obesity is associated with increased risk of wheezing in the offspring. We assessed whether impaired neonatal lung function could explain this association.We measured neonatal lung function in 2606 children of our prospective birth cohort. Information about daily symptoms of wheezing was obtained using questionnaires. Consultations and prescriptions for wheezing illnesses were derived from general practitioner patient files.Higher maternal body mass index (BMI) was associated with increased risk of wheezing in the first year of life and more consultations and prescriptions for wheezing illnesses until the age of 5 years. Lung function could partially explain the association with wheezing in the first year of life. Adding respiratory resistance to the model decreased the incidence rate ratio from 1.023 (95% CI 1.008-1.039) to 1.015 (95% CI 0.998-1.032). Anthropometrics of the 5-year-olds largely explained the association with consultations. Intermediates or confounders could not explain the association with prescriptions.There is an association between higher maternal BMI and increased risk of wheezing illnesses. In the first year of life, it is largely explained by an impaired lung function in early life, especially in children of nonatopic mothers. At the age of 5 years, infant lung function is of minor influence in this association. @ERSpublications Higher maternal BMI is associated with higher risk of wheezing illnesses partly due to impaired neonatal lung function

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“…Interestingly, several polymorphisms in linkage with LEP are associated with lung function [33]. LEP blood concentration was also shown to negatively correlate with lung function [34]. Crucially, we have biologically validated LEP upregulation in an additional donor HBECs depleted of INTS12 (Additional file 1: Figure S2).…”

Section: Resultsmentioning

confidence: 85%

“…LEP associates with the same lung function parameter as INTS12 (6, 33) albeit weaker than what was reported for 4q24 locus. Crucially LEP levels negatively correlate with lung function [34]. It is possible that reduced levels of INTS12 in specific allele carriers are responsible for elevated expression of LEP which may in turn account for reduced lung function.…”

Section: Discussionmentioning

confidence: 99%

Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways

et al. 2017

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BackgroundGenetic studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung function: GSTCD, a gene with unknown function, and/or INTS12, a member of the Integrator Complex which is currently thought to mediate 3’end processing of small nuclear RNAs.ResultsWe found that, in lung tissue, 4q24 polymorphisms associated with lung function correlate with INTS12 but not neighbouring GSTCD expression. In contrast to the previous reports in other species, we only observed a minor alteration of snRNA processing following INTS12 depletion. RNAseq analysis of knockdown cells instead revealed dysregulation of a core subset of genes relevant to airway biology and a robust downregulation of protein synthesis pathways. Consistent with this, protein translation was decreased in INTS12 knockdown cells. In addition, ChIPseq experiments demonstrated INTS12 binding throughout the genome, which was enriched in transcriptionally active regions. Finally, we defined the INTS12 regulome which includes genes belonging to the protein synthesis pathways.ConclusionINTS12 has functions beyond the canonical snRNA processing. We show that it regulates translation by regulating the expression of genes belonging to protein synthesis pathways. This study provides a detailed analysis of INTS12 activities on a genome-wide scale and contributes to the biology behind the genetic association for lung function at 4q24.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3628-3) contains supplementary material, which is available to authorized users.

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Relationship between leptin and lung function in young healthy children

Cited by 30 publications

References 13 publications

Maternal body mass index: Relation with infant respiratory symptoms and infections

Maternal body mass index: Relation with infant respiratory symptoms and infections

Maternal body mass index, neonatal lung function and respiratory symptoms in childhood

Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways

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