PP07-3 Isocaloric Fructose Restriction for 10 Days Reduces Hepatic De Novo Lipogenesis and Liver Fat in Obese Latino and African American Children

Program: Abstracts - Orals, Poster Previews, and Posters
Session: PP07-Obesity: Clinical Studies
Thursday, March 5, 2015: 11:15 AM-11:30 AM
Room 29 (San Diego Convention Center)

Poster Board THR-549
Jean-Marc Schwarz, PhD1, Susan M Noworolski, PhD2, Michael J Wen, MS3, Grace Marie Jones, PHD1, Ewan Sinclair, PhD1, Artem Dyachenco, MS1, Viva Tai, RD, MPH3, Moises Velasco Alin, BS1, Ayca Erkin-Cakmak, MD, MPH3, Alejandro Gugliucci, MD, PHD1, Kathleen Mulligan, PhD3 and Robert H Lustig, MD, MSL4
1Touro University California, Vallejo, 2University of California San Francisco, San Francisco, 3University of California San Francisco, 4University of California - San Francisco, San Francisco, CA
Background: Previous studies have shown that high sugar (specifically fructose) consumption is associated with liver fat accumulation and/or hypertriglyceridemia, which may increase risk for Type 2 diabetes and cardiovascular disease. The conversion of sugar to fat in the liver (hepatic de novolipogenesis [DNL]) may be an important pathogenic mechanism.

Objective: To determine the effect of 10 days of a fructose- but not calorie- restricted diet on DNL in obese Latino and African American children with high habitual dietary sugar intake.

Design/Methods: Latino (8F, 9M) and African American (4F, 1M) children (ages 9-18; BMI z-score 2.4 ± 0.1), who were high dietary sugar consumers at baseline (average fructose intake >50 g/day), had all meals provided for 10 days with the same caloric and macronutrient composition as their standard diet, but with other carbohydrate substituted for sugar. Subjects were weighed daily and diets adjusted to maintain baseline weight. Fractional DNL and DNL area under the curve (DNL-AUC) were measured over 8 hours of test meal feeding on Day 0 (high fructose) and Day 10 (low fructose). Test meals contained 1-13C sodium acetate tracer.  Post-prandial blood samples were analyzed by gas chromatography/mass spectrometry, and DNL calculated by mass isotopomer distribution analysis. Liver fat percentage was determined by magnetic resonance spectroscopy.

Results:DNL during feeding was significantly reduced with fructose restriction, beginning 50 minutes after initiation of tracer/feeding (2.5±0.3 vs.1.6±0.1% on days 0 and 10 respectively, P<0.003 by paired t-test) and continuing throughout the tracer/feeding procedure (13.3±1.2 vs. 5.8±0.6% at 8 hours on days 0 and 10, P<0.001).  Integrated DNL-AUC decreased by 58.7% from 53.5±6.4 on day 0 to 22.1±3.3 on day 10 (P<0.001). The decrease in DNL-AUC over only 10 days of fructose restriction was accompanied by a 29.5% reduction in liver fat from 11.9±2.3% on day 0 to 9.5±2.2% on day 10 (P <0.001; n=20). These effects remained statistically significant after adjusting by ANCOVA for minor weight loss over the 10 days (1.0±0.3 kg, P<0.001).

Conclusions: Isocaloric dietary fructose restriction for 10 days decreased hepatic DNL and liver fat in Latino and African American children irrespective of weight loss. These results suggest that hepatic DNL is an important mechanism leading to liver fat accumulation in children, which can be reversed by short-term fructose restriction. These data support public health efforts to reduce sugar consumption.

Nothing to Disclose: JMS, SMN, MJW, GMJ, ES, AD, VT, MV, AE, AG, KM, RHL

*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting

Sources of Research Support: NIH R01 DK08921, NCATS UL1 TR000004 awarded JMS and RHL