Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease

Huneault, Helaina E.; Chen, Chih-Yu; Cohen, Catherine C.; Liu, Xueyun; Jarrell, Zachery R.; He, Zhulin; DeSantos, Karla E.; Welsh, Jean A.; Maner-Smith, Kristal M.; Ortlund, Eric A.; Schwimmer, Jeffrey B.; Vos, Miriam B.

doi:10.3390/metabo14040191

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Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease

by

Helaina E. Huneault

^1,*,†,

Chih-Yu Chen

^2,†,

Catherine C. Cohen

³,

Xueyun Liu

²,

Zachery R. Jarrell

⁴,

Zhulin He

⁵

,

Karla E. DeSantos

^6,7,

Jean A. Welsh

^1,7,

Kristal M. Maner-Smith

³,

Eric A. Ortlund

²

,

Jeffrey B. Schwimmer

^8,9 and

Miriam B. Vos

^1,6,7

¹

Nutrition & Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA 30322, USA

²

Department of Biochemistry, Emory School of Medicine, Emory University, Atlanta, GA 30329, USA

³

Section of Nutrition, Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

⁴

Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, GA 30322, USA

⁵

Pediatric Biostatistics Core, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA

⁶

Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA

⁷

Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA

⁸

Department of Gastroenterology, Rady Children’s Hospital San Diego, San Diego, CA 92123, USA

⁹

Department of Pediatrics, School of Medicine, University of California, San Diego, CA 92093, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Metabolites 2024, 14(4), 191; https://doi.org/10.3390/metabo14040191

Submission received: 10 February 2024 / Revised: 21 March 2024 / Accepted: 26 March 2024 / Published: 28 March 2024

(This article belongs to the Section Lipid Metabolism)

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Abstract

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 < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (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.

Keywords: lipidomics; phospholipids; triglycerides; metabolic-dysfunction-associated steatotic liver disease (MASLD); nonalcoholic fatty liver disease (NAFLD); insulin resistance; oxylipins

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MDPI and ACS Style

Huneault, H.E.; Chen, C.-Y.; Cohen, C.C.; Liu, X.; Jarrell, Z.R.; He, Z.; DeSantos, K.E.; Welsh, J.A.; Maner-Smith, K.M.; Ortlund, E.A.; et al. Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites 2024, 14, 191. https://doi.org/10.3390/metabo14040191

AMA Style

Huneault HE, Chen C-Y, Cohen CC, Liu X, Jarrell ZR, He Z, DeSantos KE, Welsh JA, Maner-Smith KM, Ortlund EA, et al. Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites. 2024; 14(4):191. https://doi.org/10.3390/metabo14040191

Chicago/Turabian Style

Huneault, Helaina E., 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, and et al. 2024. "Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease" Metabolites 14, no. 4: 191. https://doi.org/10.3390/metabo14040191

APA Style

Huneault, H. E., Chen, C.-Y., Cohen, C. C., Liu, X., Jarrell, Z. R., He, Z., DeSantos, K. E., Welsh, J. A., Maner-Smith, K. M., Ortlund, E. A., Schwimmer, J. B., & Vos, M. B. (2024). Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease. Metabolites, 14(4), 191. https://doi.org/10.3390/metabo14040191

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Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease

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