TY - JOUR
T1 - Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity
AU - Huang, Yun
AU - Sulek, Karolina
AU - Stinson, Sara E.
AU - Holm, Louise Aas
AU - Kim, Min
AU - Trost, Kajetan
AU - Hooshmand, Kourosh
AU - Lund, Morten Asp Vonsild
AU - Fonvig, Cilius E.
AU - Juel, Helene Bæk
AU - Nielsen, Trine
AU - Ängquist, Lars
AU - Rossing, Peter
AU - Thiele, Maja
AU - Krag, Aleksander
AU - Holm, Jens Christian
AU - Legido-Quigley, Cristina
AU - Hansen, Torben
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
U2 - 10.1038/s41591-024-03279-x
DO - 10.1038/s41591-024-03279-x
M3 - Journal article
C2 - 39304782
AN - SCOPUS:85204733935
SN - 1078-8956
VL - 31
SP - 294
EP - 305
JO - Nature Medicine
JF - Nature Medicine
IS - 1
ER -