High Plasma Levels of Soluble Lectin‐like Oxidized Low‐Density Lipoprotein Receptor‐1 Are Associated With Inflammation and Cardiometabolic Risk Profiles in Pediatric Overweight and Obesity

Author:

Stinson Sara E.1ORCID,Jonsson Anna E.1ORCID,Andersen Mette K.1ORCID,Lund Morten A. V.23ORCID,Holm Louise Aas12ORCID,Fonvig Cilius E.124ORCID,Huang Yun1ORCID,Stankevič Evelina1ORCID,Juel Helene Bæk1ORCID,Ängquist Lars1ORCID,Sørensen Thorkild I. A.15ORCID,Ongstad Emily L.6ORCID,Gaddipati Ranjitha6ORCID,Grimsby Joseph67ORCID,Rhodes Christopher J.6ORCID,Pedersen Oluf1ORCID,Christiansen Michael28ORCID,Holm Jens‐Christian129ORCID,Hansen Torben1ORCID

Affiliation:

1. Novo Nordisk Foundation Center for Basic Metabolic Research Faculty of Health and Medical Sciences, University of Copenhagen Denmark

2. The Children’s Obesity Clinic, Accredited European Centre for Obesity Management, Department of Pediatrics Holbæk Hospital Holbæk Denmark

3. Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen Denmark

4. Department of Pediatrics Kolding Hospital a part of Lillebælt Hospital Kolding Denmark

5. Department of Public Health, Faculty of Health and Medical Sciences University of Copenhagen Denmark

6. Research and Early Development Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca Gaithersburg MD

7. Regeneron Pharmaceuticals, Inc. Tarrytown NY

8. Department for Congenital Disorders Statens Serum Institute Copenhagen Denmark

9. Faculty of Health and Medical Sciences University of Copenhagen Denmark

Abstract

Background Lectin‐like oxidized low‐density lipoprotein (ox‐LDL) receptor‐1 is a scavenger receptor for oxidized low‐density lipoprotein. In adults, higher soluble lectin‐like ox‐LDL receptor‐1 (sLOX‐1) levels are associated with cardiovascular disease, type 2 diabetes, and obesity, but a similar link in pediatric overweight/obesity remains uncertain. Methods and Results Analyses were based on the cross‐sectional HOLBAEK Study, including 4‐ to 19‐year‐olds from an obesity clinic group with body mass index >90th percentile (n=1815) and from a population‐based group (n=2039). Fasting plasma levels of sLOX‐1 and inflammatory markers were quantified, cardiometabolic risk profiles were assessed, and linear and logistic regression analyses were performed. Pubertal/postpubertal children and adolescents from the obesity clinic group exhibited higher sLOX‐1 levels compared with the population ( P <0.001). sLOX‐1 positively associated with proinflammatory cytokines, matrix metalloproteinases, body mass index SD score, waist SD score, body fat %, plasma alanine aminotransferase, serum high‐sensitivity C‐reactive protein, plasma low‐density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure SD score, and inversely associated with plasma high‐density lipoprotein cholesterol (all P <0.05). sLOX‐1 positively associated with high alanine aminotransferase (odds ratio [OR], 1.16, P =4.1 E‐04), insulin resistance (OR, 1.16, P =8.6 E‐04), dyslipidemia (OR, 1.25, P =1.8 E‐07), and hypertension (OR, 1.12, P =0.02). Conclusions sLOX‐1 levels were elevated during and after puberty in children and adolescents with overweight/obesity compared with population‐based peers and associated with inflammatory markers and worsened cardiometabolic risk profiles. sLOX‐1 may serve as an early marker of cardiometabolic risk and inflammation in pediatric overweight/obesity. Registration The HOLBAEK Study, formerly known as The Danish Childhood Obesity Biobank, ClinicalTrials.gov identifier number NCT00928473, https://clinicaltrials.gov/ct2/show/NCT00928473 (registered June 2009).

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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