The Role of Leptin and Other Hormones Related to Bone Metabolism and Appetite Regulation as Determinants of Gain in Body Fat and Fat-Free Mass in 8–11-Year-Old Children

Dalskov, Stine-Mathilde; Ritz, Christian; Larnkjær, Anni; Damsgaard, Camilla T.; Petersen, Randi; Sørensen, Louise Bergmann; Ong, Kenneth; Astrup, Arne; Mølgaard, Christian; Michaelsen, Kim F.

doi:10.1210/jc.2014-3706

Cited by 9 publications

(3 citation statements)

References 43 publications

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“…When comparing our findings with studies in healthy, term‐born children of similar age, there are resemblances as well as contrasts. Leptin and IGF‐1 have been positively associated with FM index in children aged 8‐11 years . We demonstrated a similar relation between leptin, IGF‐1 and FM, although the latter was not adjusted for height.…”

Section: Discussionsupporting

confidence: 64%

“…The association between leptin and FM has been extensively described, although predominantly in adult, obese populations. In term‐born children at school age, leptin has also been positively associated with FM index (ie FM adjusted for height) . We showed that this association was also present in preterm‐born children at term age and 6‐month corrected age (CA, ie calculated from term age) …”

Section: Introductionmentioning

confidence: 62%

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Leptin and IGF‐1 in relation to body composition and bone mineralization of preterm‐born children from infancy to 8 years

Ruys

Lagemaat

Lafeber

et al. 2018

Clinical Endocrinology

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Funding informationThe original randomized controlled trial was supported by an unrestricted research grant from Friesland Campina, Amersfoort, the Netherlands. Friesland Campina also provided the formulas. CR was supported by an unrestricted research grant, provided by Hero Benelux, Breda, the Netherlands. Neither Friesland Campina nor Hero Benelux had a role in the design and execution of the studies, or in the analysis and interpretation of the results. SummaryObjective: Preterm birth has been associated with altered body composition, especially increased fat mass (FM) and decreased bone mineralization, and leptin and IGF-1 have been suggested to be involved in the regulation of both. We aimed to study the interplay between leptin, IGF-1, FM and bone mineralization measured in infancy and childhood of children born preterm. Design: Observational study.Patients/subjects: Seventy-nine (40 boys) preterm-born children (gestational age ≤32 weeks and/or birth weight ≤1500 g) aged 8 years.Measurements: Serum leptin and IGF-1 were measured at term age, at 3-and 6-month corrected age (CA), and 8 years. Body composition (fat and lean mass) and bone parameters (bone area, mineral content and density) were measured by Dualenergy X-ray Absorptiometry (DXA) at term age, 6-month CA and 8 years.Results: Leptin was positively associated with FM at all time points and with bone parameters at term age and 6-month CA. IGF-1 was associated with body composition and bone density at most of the time points. Explained variation in bone mineralization increased significantly by adding bone area (BA) and height to the models. Conclusions:During infancy and childhood, leptin and IGF-1 were associated with body composition in preterm-born children. In addition, leptin was associated with bone parameters in early infancy, but not in childhood. It is hypothesized that a complicated interplay between multiple pathways, which most likely changes over time, is involved in regulation of body composition and bone mineralization of pretermborn infants. K E Y W O R D Sbone mineralization, fat mass, follow-up, IGF-1, leptin, preterm infants

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 62%

Leptin and IGF‐1 in relation to body composition and bone mineralization of preterm‐born children from infancy to 8 years

Ruys

Lagemaat

Lafeber

et al. 2018

Clinical Endocrinology

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“…The precise relationship plasma leptin effects on bone remodeling may in fact be dose -dependent and bimodal, producing opposite effects of stimulation and suppression dependent upon its levels (Kim et al, 2010;Motyl and Rosen 2012). Effects are also suggested to be sex-specific (Dalskov et al, 2015) Much work is needed with…”

Section: Discussionmentioning

confidence: 99%

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Mosher¹,

Melton²,

Stapleton³

et al. 2016

Human Biology

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DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA which are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process.Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative function includes regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism and Pre-print version. Visit http://digitalcommons.wayne.edu/humbiol/ after publication to acquire the final version.reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examines the significance of variation in DNA methylation patterns along the leptin core promoter in four populations and uses biomarkers reflecting leptin's functional process in two of those populations to investigate the relevance of the ethnic variation identified in the DNA methylation. Those two populations are the Western Buryats of Siberia and the Mennonites of Central Kansas.LEP's core promoter region contains both the C/EBPα transcription binding site (TBS) which tempers the final step in adipocyte maturity and capacity to synthesize leptin and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, with others suggesting tissue-specific methylation variation at this region. We hypothesize that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers which reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system and anthropometric measures.A distinct and consistent overall pattern of differential DNA methylation across seven CpG sites of LEP core promoter is documented in all ethnicities and both sexes in our combined analyses of 313 individuals. This pattern replicates those identified in previous studies, thus suggesting a conserved core promoter region across populations. The second analyses in two of the four ...

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Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children

et al. 2015

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The Role of Leptin and Other Hormones Related to Bone Metabolism and Appetite Regulation as Determinants of Gain in Body Fat and Fat-Free Mass in 8–11-Year-Old Children

Abstract: Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.

Cited by 9 publications

References 43 publications

Leptin and IGF‐1 in relation to body composition and bone mineralization of preterm‐born children from infancy to 8 years

Leptin and IGF‐1 in relation to body composition and bone mineralization of preterm‐born children from infancy to 8 years

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children

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