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

• Type of Material: Article
• Authors: Catherine C Cohen, Emory University; Kelvin W Li, University of California Berkeley; Adina Alazraki, Emory University; Carine Beysen, Fluxbio, San Mateo, California; Carissa A Carrier, School of Medicine, UCSD; Rebecca L Cleeton, Emory University; Mohamad Dandan, University of California Berkeley; Janet Figueroa, Emory University; Jack Knight-Scott, Childrens Healthcare Atlanta; Cynthia J Knott, School of Medicine, UCSD; Kimberly P Newton, School of Medicine, UCSD; Edna M Nyangau, University of California Berkeley; Claude B Sirlin, School of Medicine, UCSD; Patricia A Ugalde-Nicalo, School of Medicine, UCSD; Jean Welsh, Emory University; Mark K Hellerstein, University of California Berkeley; Jeffrey B Schwimmer, School of Medicine, UCSD; Miriam Vos, Emory University
• Language: English
• Date: 2021-12-15
• Publisher: AMER SOC CLINICAL INVESTIGATION INC
• Publication Version: Final Published Version
• Copyright Statement: © 2021 American Society for Clinical Investigation
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/JCI150996
• Title of Journal or Parent Work: JOURNAL OF CLINICAL INVESTIGATION
• Volume: 131
• Issue: 24
• Grant/Funding Information: Made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors
• Keywords: Science & Technology; INDIVIDUALS; Medicine, Research & Experimental; Research & Experimental Medicine; HUMANS; GLUCOSE-PRODUCTION; CHILDREN; FRUCTOSE; ENERGY-INTAKE; OXIDATION; INSULIN-RESISTANCE; Life Sciences & Biomedicine; ORAL GLUCOSE; DEPOSITION
• Research Categories: Health Sciences, Radiology; Health Sciences, Nutrition

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.