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Abstract Details
Dietary sugar restriction reduces hepatic de novo lipogenesis in adolescent boys with fatty liver disease
J Clin Invest. 2021 Dec 15;131(24):e150996. doi: 10.1172/JCI150996.
Catherine C Cohen12, Kelvin W Li3, Adina L Alazraki45, Carine Beysen6, Carissa A Carrier7, Rebecca L Cleeton1, Mohamad Dandan3, Janet Figueroa1, Jack Knight-Scott5, Cynthia J Knott8, Kimberly P Newton79, Edna M Nyangau3, Claude B Sirlin10, Patricia A Ugalde-Nicalo79, Jean A Welsh111, Marc K Hellerstein3, Jeffrey B Schwimmer79, Miriam B Vos111
Author information
Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia, USA.
Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, California, USA.
Department of Radiology, School of Medicine, Emory University, Atlanta, Georgia, USA.
Department of Radiology, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Fluxbio, San Mateo, California, USA.
Department of Pediatrics, School of Medicine, UCSD, La Jolla, California, USA.
Altman Clinical and Translational Research Institute, School of Medicine, UCSD, La Jolla, California, USA.
Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California, USA.
Liver Imaging Group, Department of Radiology, UCSD, La Jolla, California, USA.
Department of Gastroenterology, Hepatology, and Nutrition, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Abstract
BACKGROUNDHepatic 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.METHODSAdolescent 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.RESULTSHepatic 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).CONCLUSIONOur 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.TRIAL REGISTRYClinicalTrials.gov NCT02513121.FUNDINGThe Nutrition Science Initiative (made possible by gifts from the Laura and John Arnold Foundation, Ambrose Monell Foundation, and individual donors), the UCSD Altman Clinical and Translational Research Institute, the NIH, Children's Healthcare of Atlanta and Emory University's Children's Clinical and Translational Discovery Core, Children's Healthcare of Atlanta and Emory University Pediatric Biostatistical Core, the Georgia Clinical and Translational Science Alliance, and the NIH National Institute of Diabetes, Digestive, and Kidney Disease.