Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity

Abstract

Background & aims: Consumption of sugar is associated with obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis [DNL]) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/d).

Methods: Children (9-18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child.

Results: Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (interquartile range [IQR], 2.5%-14.8%) to 3.8% (IQR, 1.7%-15.5%) (P < .001) and VAT decreased from 123 cm3 (IQR, 85-145 cm3) to 110 cm3 (IQR, 84-134 cm3) (P < .001). The DNL area under the curve decreased from 68% (IQR, 46%-83%) to 26% (IQR, 16%-37%) (P < .001). Insulin kinetics improved (P < .001). These changes occurred irrespective of baseline liver fat.

Conclusions: Short-term (9 days) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov Number: NCT01200043.

Keywords: Dietary Treatment; NAFLD; Overweight; Pediatric.

Conflict of interest statement

Conflicts of Interest: SMN receives funding from Gilead Sciences, Inc. and from Verily Life Sciences for projects outside the submitted work. RHL wrote a book on obesity for the general public in 2012. All other authors report no conflicts of interest.

Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Clinical research design and procedures on day 0 and day 10, depicting the time of oral glucose tolerance testing (OGTT), MR studies, and sodium [1-13C]-acetate administration via liquid meals (shakes) to determine rate of de novo lipogenesis (DNL).

Figure 2

Changes in individual fat compartments in obese children (2A–2D) before and after nine days of isocaloric fructose restriction, and in the subset of 9 children who did not lose weight (2E–2H) during fructose restriction. Figs 2A and 2E depict average changes (mean ± SEM) in liver fat as determined by MR, and visceral (VAT) and subcutaneous (SAT) fat as determined by MR in the entire cohort (2A) and the subgroup of 9 participants who did not lose weight (2E). Figs 2B and 2F depict individual serial measures of liver fat in the entire cohort (2B) and the subgroup of 9 participants who did not lose weight (2F). Figs 2C and 2G depict individual serial measures of VAT. Figs 2D and 2H depict individual serial measures of SAT in the entire cohort (2D) and the subgroup of 9 participants who did not lose weight (2H). Open and closed circles to the left and right of the day 0 and day 10 individual plots depict median and interquartile range (Figs 3B and 3F) or mean ± SEM (Figs 3C, 3D, 3G, 3H). Decreases in liver fat and VAT were statistically significant in the group as a whole (P

Figure 3

Changes in postprandial fractional de novo lipogenesis (DNL; percent of palmitate in circulating triglyceride that was synthesized de novo) and the integrated DNL-area under the curve (AUC) on days 0 (open circles) and 10 (closed circles) after isocaloric fructose restriction in 40 obese children (3A and 3B), and in the subgroup of 9 children who did not lose weight (3C and 3D) during fructose restriction. On both study days, after an overnight fast, and after the OGTT was complete, participants consumed liquid meals every 20 minutes for six hours, starting at 10:30 AM. Blood samples were obtained hourly during this period. Figs 3A and 3C depict fractional DNL (mean ± SEM) for all subjects (3A) and the subgroup of 9 participants who did not lose weight (3C). Figs 3B and 3D depict individual serial measures of DNL-AUC in the group as a whole (3B) and the subgroup who did not lose weight (3D). Decreases in DNL-AUC were statistically significant in the group as a whole (P<0.001) as well as the subgroup who did not lose weight (P=0.006).