Nutrients

2072-66431472022Mar30NutrientsNutrientsEffects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity.143210.3390/nu14071432Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (-0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.OlsonEmilyEDepartment of Pediatrics, George Washington University, Children's National Hospital, Washington, DC 20010, USA.SuhJung HJHChildren's Hospital Oakland Research Institute, University of California Benioff Children's Hospital Oakland, Oakland, CA 94609, USA.SchwarzJean-MarcJMDepartment of Basic Sciences, Touro University California, Vallejo, CA 94592, USA.NoworolskiSusan MSMDepartment of Radiology, University of California San Francisco, San Francisco, CA 94143, USA.JonesGrace MGM0000-0003-1106-0626Department of Basic Sciences, Touro University California, Vallejo, CA 94592, USA.BarberJohn RJRClinical and Translational Science Institute, Children's National Hospital, Washington, DC 20010, USA.Erkin-CakmakAycaADepartment of Pediatrics, Division of Endocrinology, University of California San Francisco Benioff Children's Hospital, San Francisco, CA 94143, USA.MulliganKathleenKDepartment of Medicine, Division of Endocrinology and Metabolism, University of California San Francisco, San Francisco, CA 94110, USA.LustigRobert HRH0000-0001-6983-2639Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA.Mietus-SnyderMicheleM0000-0003-2791-9896Department of Pediatrics, Children's National Hospital, Division of Cardiology, George Washington University, Washington, DC 20010, USA.engP30 DK098722DKNIDDK NIH HHSUnited StatesClinical TrialJournal Article20220330