Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity

Authors

Emily Olson, Department of Pediatrics, George Washington University, Children's National Hospital, Washington, DC 20010, USA.
Jung H. Suh, Children's Hospital Oakland Research Institute, University of California Benioff Children's Hospital Oakland, Oakland, CA 94609, USA.
Jean-Marc Schwarz, Department of Basic Sciences, Touro University California, Vallejo, CA 94592, USA.
Susan M. Noworolski, Department of Radiology, University of California San Francisco, San Francisco, CA 94143, USA.
Grace M. Jones, Department of Basic Sciences, Touro University California, Vallejo, CA 94592, USA.
John R. Barber, Clinical and Translational Science Institute, Children's National Hospital, Washington, DC 20010, USA.
Ayca Erkin-Cakmak, Department of Pediatrics, Division of Endocrinology, University of California San Francisco Benioff Children's Hospital, San Francisco, CA 94143, USA.
Kathleen Mulligan, Department of Medicine, Division of Endocrinology and Metabolism, University of California San Francisco, San Francisco, CA 94110, USA.
Robert H. Lustig, Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA.
Michele Mietus-Snyder, Department of Pediatrics, Children's National Hospital, Division of Cardiology, George Washington University, Washington, DC 20010, USA.

Document Type

Journal Article

Publication Date

3-30-2022

Journal

Nutrients

Volume

14

Issue

7

DOI

10.3390/nu14071432

Keywords

cardiometabolic risk; childhood obesity; insulin sensitivity; sphingolipid ceramide

Abstract

Sugar 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.

APA Citation

Olson, Emily; Suh, Jung H.; Schwarz, Jean-Marc; Noworolski, Susan M.; Jones, Grace M.; Barber, John R.; Erkin-Cakmak, Ayca; Mulligan, Kathleen; Lustig, Robert H.; and Mietus-Snyder, Michele, "Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity" (2022). GW Authored Works. Paper 520.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/520

Department

Pediatrics