Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity
Yun Huang, Karolina Sulek, Sara Stinson, Louise Aas Holm, Min Kim, Kajetan Trôst, Kourosh Hooshmand, Morten Asp Vonsild Lund, Cilius Esmann Fonvig, Helene Bæk Juel, Trine Nielsen, Lars Ängquist, Peter Rossing, Maja Thiele, Aleksander Krag, Jens‐Christian Holm, Cristina Legido‐Quigley, Torben Hansen
Abstract
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. A combination of cross-sectional study and lifestyle intervention program uncovered altered lipid profiles in children and adolescents with obesity and demonstrated that a personalized obesity management program can restore a healthy lipid profile.