Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease
Helaina E. Huneault,
Chih-Yu Chen,
Catherine C. Cohen,
Xueyun Liu,
Zachery R. Jarrell,
Zhulin He,
Karla E. DeSantos,
Jean A. Welsh,
Kristal M. Maner-Smith,
Eric A. Ortlund,
Jeffrey B. Schwimmer,
Miriam B. Vos
Affiliations
Helaina E. Huneault
Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA
Chih-Yu Chen
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA
Catherine C. Cohen
Section of Nutrition, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Xueyun Liu
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA
Zachery R. Jarrell
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, GA 30322, USA
Zhulin He
Pediatric Biostatistics Core, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA
Karla E. DeSantos
Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA
Jean A. Welsh
Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA
Kristal M. Maner-Smith
Section of Nutrition, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Eric A. Ortlund
Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA
Jeffrey B. Schwimmer
Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, CA 92123, USA
Miriam B. Vos
Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA
Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11–16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.
