Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity
Pediatric obesity is a progressive, chronic disease that can lead to serious cardiometabolic complications. Here we investigated the peripheral lipidome in 958 children and adolescents with overweight or obesity and 373 with normal weight, in a cross-sectional study. We also implemented a family-based, personalized program to assess the effects of obesity management on 186 children and adolescents in a clinical setting. Using mass spectrometry-based lipidomics, we report an increase in ceramides, alongside a decrease in lysophospholipids and omega-3 fatty acids with obesity metabolism. Ceramides, phosphatidylethanolamines and phosphatidylinositols were associated with insulin resistance and cardiometabolic risk, whereas sphingomyelins showed inverse associations. Additionally, a panel of three lipids predicted hepatic steatosis as effectively as liver enzymes. Lipids partially mediated the association between obesity and cardiometabolic traits. The nonpharmacological management reduced levels of ceramides, phospholipids and triglycerides, indicating that lowering the degree of obesity could partially restore a healthy lipid profile in children and adolescents.
Authors
- Yun Huang (ORCID: https://orcid.org/0000-0002-3064-6641)
- Karolina Sulek (ORCID: https://orcid.org/0000-0002-7117-3756)
- Sara Stinson (ORCID: https://orcid.org/0000-0002-1491-9179)
- Jens‐Christian Holm (ORCID: https://orcid.org/0000-0003-4653-342X)
- Trine Nielsen (ORCID: https://orcid.org/0000-0002-2066-7895)
- Louise Aas Holm (ORCID: https://orcid.org/0000-0002-5439-5429)
- Helene Bæk Juel (ORCID: https://orcid.org/0000-0002-5763-8545)
- Aleksander Krag (ORCID: https://orcid.org/0000-0002-9598-4932)
- Kajetan Trôst (ORCID: https://orcid.org/0000-0002-3863-5269)
- Morten Asp Vonsild Lund (ORCID: https://orcid.org/0000-0002-2711-1259)
- Cristina Legido‐Quigley (ORCID: https://orcid.org/0000-0002-4018-214X)
- Lars Ängquist (ORCID: https://orcid.org/0000-0002-9516-4424)
- Maja Thiele (ORCID: https://orcid.org/0000-0003-1854-1924)
- Peter R Rossing (ORCID: https://orcid.org/0000-0002-1531-4294)
- Cilius Esmann Fonvig (ORCID: https://orcid.org/0000-0002-5031-0125)
- Min Kim (ORCID: https://orcid.org/0000-0002-8769-4804)
- Torben Hansen (ORCID: https://orcid.org/0000-0001-8748-3831)
- Kourosh Hooshmand
Institutions
- University of Copenhagen (DK)
- Steno Diabetes Centers (DK)
- University of Southern Denmark (DK)
- King's College London (GB)
- Novo Nordisk Foundation (DK)
- Odense University Hospital (DK)
- Copenhagen University Hospital (DK)
- Zealand University Hospital (DK)
- European Association for the Study of Obesity (GB)
- Holbæk Sygehus (DK)
Publication Details
- Journal
- Nature Medicine
- Published
- 2024-09-20
- DOI
- https://doi.org/10.1038/s41591-024-03279-x
- Citations
- 50
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 19.33
Funders
- Innovationsfonden
- Lundbeckfonden
- Novo Nordisk Fonden