Evidence map›Paper›PMID 41826632›Full record

ArticleInternational journal of obesity (2005)2026

Inversed impaired osteogenic activity in children with severe obesity due to MC4R deficiency compared to LEP and LEPR deficiency.

Qasim M Janjua, Roohia Khanam, Sadia Saeed, Jaida Manzoor, Attiya Haseeb, Sharoon Hanook, Amelie Bonnefond, Muhammad Arslan, Philippe Froguel

Abstract read
In one paragraph

Article in International journal of obesity (2005), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Qasim M Janjua *Department of Physiology and Biophysics, College of Medicine and Health Sciences, National University of Science and Technology, Sohar, Oman.ORCID 0000-0001-7896-8802
Roohia Khanam *KAM School of Life Sciences, Forman Christian College, Lahore, Pakistan.ORCID 0000-0001-6826-7471
Sadia SaeedInserm UMR 1283, CNRS UMR 8199, EGID, Institut Pasteur de Lille, Lille, France.ORCID 0000-0003-3144-7772
Jaida ManzoorDepartment of Paediatric Endocrinology, Children's Hospital, Lahore, Pakistan.
Attiya HaseebKAM School of Life Sciences, Forman Christian College, Lahore, Pakistan.
Sharoon HanookDepartment of Statistics, Forman Christian College, Lahore, Pakistan.
Amelie BonnefondInserm UMR 1283, CNRS UMR 8199, EGID, Institut Pasteur de Lille, Lille, France.
Muhammad ArslanKAM School of Life Sciences, Forman Christian College, Lahore, Pakistan. muhammadarslan@fccollege.edu.pk.ORCID 0000-0003-3227-0024
Philippe FroguelInserm UMR 1283, CNRS UMR 8199, EGID, Institut Pasteur de Lille, Lille, France. p.froguel@imperial.ac.uk.ORCID 0000-0003-2972-0784

Funding

Medical Research Council (MRC) MR/S026193/1
6 · The paper itself

Abstract

objectiveChronic obesity is associated with impaired bone health. However, few investigations have been conducted to assess bone physiology in early-onset obesity. In this study, we measured specific bone turnover and metabolic biomarkers in children with severe obesity with biallelic loss-of-function variants of the leptin (LEP), leptin receptor (LEPR), or melanocortin 4 receptor (MC4R) genes.

methodsThirty-nine children aged 0.3-8.8 years with a BMI SDS ≥ 3, previously identified with pathogenic variants in LEP, LEPR, or MC4R, were recruited for the current study. Additionally, 13 age-matched children with severe obesity who tested negative for variants in known obesity-related genes were included, and another 13 unrelated age-matched children with normal body weight served as the control group. Serum osteocalcin, osteopontin, osteoprotegerin, and sclerostin levels were assessed using multi-analyte profiling. Serum leptin, insulin, and cortisol levels were determined using ELISA.

resultsSerum levels of osteocalcin and osteopontin, specific markers of bone formation, were significantly lower in children with LEP and LEPR biallelic variants than in the control group. In contrast, the values of these two biomarkers in children with MC4R deficiency were significantly higher than those in the other groups. No differences were observed in the bone resorption markers osteoprotegerin and sclerostin. Hyperleptinemia was more pronounced in children with LEPR deficiency. Serum insulin concentrations were elevated in individuals with MC4R deficiency, whereas serum cortisol levels were significantly higher in children with LEP deficiency than in all other groups.

conclusionOur data demonstrate that osteogenic activity (but not resorption activity) is differentially affected in children with complete genetic disruption of the leptin-signaling pathway. Children with MC4R deficiency showed higher osteogenic markers, but children with LEP and LEPR deficiencies showed the opposite. Our results support the usefulness of bone turnover biomarkers for the assessment and management of bone health in different types of obesity.

Indexed as

LeptinObesity, MorbidOsteogenesisPediatric ObesityReceptor, Melanocortin, Type 4Receptors, LeptinBiomarkersChildChild, PreschoolFemaleHumansInfantMaleOsteocalcinBiomarkersLEP protein, humanLEPR protein, humanLeptinMC4R protein, humanOsteocalcinReceptor, Melanocortin, Type 4Receptors, LeptinBone metabolism biomarkersLEPLEPR MC4R.Monogenic obesity

Identifiers

PMID41826632
PMCPMC13286991

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.