Original Article

International Journal of Obesity accepted article preview 17 August 2017; doi: 10.1038/ijo.2017.201

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Untargeted metabolomics identifies a plasma sphingolipid-related signature associated with lifestyle intervention in prepubertal children with obesity

M J Leal-Witt1,2,6, M Ramon-Krauel1,2,6, S Samino3,4, M Llobet1,2, D Cuadras5, J C Jimenez-Chillaron1,2, O Yanes3,4 and C Lerin1,2

  1. 1Endocrinology Department, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
  2. 2Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
  3. 3Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili, Tarragona, Spain
  4. 4Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
  5. 5Statistics Department, Sant Joan de Déu Research Foundation, Barcelona, Spain

Correspondence: Dr C Lerin, Endocrinology department, Institut de Recerca Sant Joan de Déu, c/Santa Rosa 39, Barcelona 08950, Spain. E-mail: clerin@fsjd.org

6These authors contributed equally to this work.

Received 27 March 2017; Revised 25 July 2017; Accepted 2 August 2017
Accepted article preview online 17 August 2017

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Abstract

OBJECTIVE:

 

Childhood obesity is a strong risk factor for adult obesity and metabolic diseases, including type 2 diabetes and cardiovascular disease. Early lifestyle intervention in children with obesity reduces future disease risk. The objective of this study is to identify metabolic signatures associated with lifestyle intervention in prepubertal children with obesity.

METHODS:

 

Thirty-five prepubertal children (7–10 years) with obesity (BMI>2 standard deviations) were enrolled in the study and participated in a 6-month-long lifestyle intervention program. Physiological and biochemical data and blood samples were collected both at baseline and after the intervention. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach was applied to obtain a comprehensive profiling of plasma samples, identifying 2581 distinct metabolite. Principal component analysis (PCA) was performed to consolidate all features into 8 principal components. Associations between metabolites and physiological and biochemical variables were investigated.

RESULTS:

 

The intervention program significantly decreased mean (95% CI) BMI standard deviation score from 3.56 (3.29–3.84) to 3.11 (2.88–3.34) (P<0.001). PCA identified one component (PC1) significantly altered by the intervention (Bonferroni adjusted P=0.008). A sphingolipid metabolism-related signature was identified as the major contributor to PC1. Sphingolipid metabolites were decreased by the intervention, and included multiple sphingomyelin, ceramide, glycosylsphingosine, and sulfatide species. Changes in several sphingolipid metabolites were associated with intervention-induced improvements in HbA1c levels.

CONCLUSIONS:

 

Decreased circulating sphingolipid-related metabolites were associated with lifestyle intervention in prepubertal children with obesity, and correlated to improvements in HbA1c.

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