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

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. TRIAL REGISTRY. ClinicalTrials.gov NCT02513121.

Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity

“…There are several limitations to this study. There was no external control group; on the other hand, five separate internal controls validated our results [ 16 ], and our original results have been corroborated by other investigators [ 50 , 51 ]. The sample size is relatively small and the dietary intervention was only nine days in duration.…”

Dietary Counseling Aimed at Reducing Sugar Intake Yields the Greatest Improvement in Management of Weight and Metabolic Dysfunction in Children with Obesity

“…This is based on the studies in humans [ 27 ] and rodents [ 28 ], showing that fructose, but not equicaloric glucose intake, leads to development of metabolic complications. The pathways affected by fructose metabolism include insulin resistance [ 29 ], decreased fatty acid oxidation [ 30 , 31 ], and increased hepatic de novo lipogenesis [ 32 , 33 ], all of which contribute to fat accumulation. Mechanistically, these processes lead to inflammation [ 34 ], lipotoxicity [ 35 ], endoplasmic reticulum stress [ 36 ], advanced glycation end products [ 37 ], and others, which have been proposed to be the mediators of metabolic complications.…”

“…Similarly, AST was not different between responders and non-responders ( p = 0.21). A recent study in children examined the effects of eight weeks of dietary sugar restriction and documented a reduction in ALT, as well as a decrease in hepatic de novo lipogenesis [ 33 ]. The difference between this study and ours may be that we did not specifically focus our dietary guidance on restricting fructose intake.…”

Metabolome Alterations Linking Sugar-Sweetened Beverage Intake with Dyslipidemia in Youth: The Exploring Perinatal Outcomes among CHildren (EPOCH) Study

“…SSB intake has also been associated with cardiometabolic risk factors in childhood and adolescence, including markers of insulin resistance, inflammation, and dyslipidemia, independent of energy intake [5][6][7][8][9][10]. Proposed mechanisms include the higher glycemic index of SSBs, which may contribute to an increased insulin secretory response [11], or associations of added sugars in SSBs, especially fructose, with hepatic de novo lipogenesis and ectopic liver fat [12][13][14][15][16], an effect that has been observed even when weight is held stable [13]. A critical future direction is, therefore, better understanding the pathophysiological disturbances associated with SSBs, as this may also shed light on objective biomarkers of intake of SSBs, a food group for which social norms may bias self-reported intake data.…”