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Author Notes:

Miriam B. Vos, MD, MSPH, Department of Pediatrics, Emory University, 1760 Haygood Drive NE, Atlanta, Georgia 30322, USA. Phone: 404.727.9930; Email: mvos@emory.edu

CCC, MBV, JBS, KWL, CB, and MKH designed the study. MBV, JBS, PAUN, JAW, KPN, and CJK designed the original intervention trial. KWL, CB, MD, EMN, and MKH designed the tracer protocol and performed sample analyses. ALA, CAC, RLC, JKS, and CBS assisted with data acquisition and provided administrative or technical support. CCC performed data analyses. JF provided statistical support. CCC, KWL, CB, MKH, and MBV interpreted the data and wrote the manuscript. MBV and JBS acquired funding. All authors critically reviewed and edited the manuscript, and approve of the final manuscript.

The authors thank the study subjects and their families for their participation. The authors also acknowledge Scott Turner for his assistance in designing the stable isotope tracer study and in the correlation study of DNL in VLDL-TG and plasma TG. The authors also acknowledge the research coordinators, staff, and technicians who were involved in carrying out the intervention and data collection. This study was supported by foundational grant funding from the Nutrition Science Initiative (made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors); support from the UCSD Altman Clinical and Translational Research Institute; grants UL1TR001442 and UL1TR002378 from the NIH; support from the Children’s Healthcare of Atlanta and Emory University’s Children’s Clinical and Translational Discovery Core; support from the Children’s Healthcare of Atlanta and Emory University Pediatric Biostatistical Core; and support from the Georgia Clinical and Translational Science Alliance. CCC is currently supported by NIH National Institute of Diabetes, Digestive, and Kidney Diseases grant no. T32DK07658.

JBS has received research support from Galmed, Intercept, Genfit, and Seraphina. CBS has served as a consultant representative of the University of California Regents for GE Healthcare, Bayer, Boehringer Ingelheim, AMRA, Fulcrum Therapeutics, Medscape, and Resoundant; has served on scientific advisory boards for AMRA, Guerbet, and VitualScopics; is receiving research grants from ACR Innovation, Bayer, Gilead, GE Healthcare, General Electric, Philips, and Siemens; has served as a consultant for AMRA, Boehringer Ingelheim, Epigenomics, and Guerbet; has served on the speaker’s bureau for Resoundant and General Electric; has laboratory service agreements with Enanta, Genzyme, Gilead, Icon Medical Imaging, Intercept, Janssen, NuSirt, Shire, Synageva, Takeda, and VitualScopics; has received royalties from Wolters Kluwer for educational materials; serves on the advisory board for Quantix Bio; and owns stock options in Livivos. MBV has received grant support from Resonance Health, Immuron, Gemphire, Shire, and Target Pharmasolutions; and personal fees from AMRA, Immuron, Intercept, Target Pharmasolutions, Shire, Bristol-Myers Squibb, Boehringer Ingelheim, and Axcella Health.

Subjects:

Research Funding:

Made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • INSULIN-RESISTANCE
  • GLUCOSE-PRODUCTION
  • ENERGY-INTAKE
  • ORAL GLUCOSE
  • FRUCTOSE
  • CHILDREN
  • INDIVIDUALS
  • DEPOSITION
  • OXIDATION
  • HUMANS

Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease

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Journal Title:

JOURNAL OF CLINICAL INVESTIGATION

Volume:

Volume 131, Number 24

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

BACKGROUND. Hepatic de novo lipogenesis (DNL) is elevated in nonalcoholic fatty liver disease (NAFLD). Improvements in hepatic fat by dietary sugar reduction may be mediated by reduced DNL, but data are limited, especially in children. We examined the effects of 8 weeks of dietary sugar restriction on hepatic DNL in adolescents with NAFLD and correlations between DNL and other metabolic outcomes. METHODS. Adolescent boys with NAFLD (n = 29) participated in an 8-week, randomized controlled trial comparing a diet low in free sugars versus their usual diet. Hepatic DNL was measured as percentage contribution to plasma triglyceride palmitate using a 7-day metabolic labeling protocol with heavy water. Hepatic fat was measured by magnetic resonance imaging–proton density fat fraction. RESULTS. Hepatic DNL was significantly decreased in the treatment group (from 34.6% to 24.1%) versus the control group (33.9% to 34.6%) (adjusted week 8 mean difference: –10.6% [95% CI: –19.1%, –2.0%]), which was paralleled by greater decreases in hepatic fat (25.5% to 17.9% vs. 19.5% to 18.8%) and fasting insulin (44.3 to 34.7 vs. 35.5 to 37.0 μIU/ mL). Percentage change in DNL during the intervention correlated significantly with changes in free-sugar intake (r = 0.48, P = 0.011), insulin (r = 0.40, P = 0.047), and alanine aminotransferase (ALT) (r = 0.39, P = 0.049), but not hepatic fat (r = 0.13, P = 0.532). CONCLUSION. Our results suggest that dietary sugar restriction reduces hepatic DNL and fasting insulin, in addition to reductions in hepatic fat and ALT, among adolescents with NAFLD. These results are consistent with the hypothesis that hepatic DNL is a critical metabolic abnormality linking dietary sugar and NAFLD.

Copyright information:

© 2021 American Society for Clinical Investigation

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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