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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 153; no. 3; pp. 743 - 752
• Main Authors: Schwarz, Jean-Marc, Noworolski, Susan M, Erkin-Cakmak, Ayca, Korn, Natalie J, Wen, Michael J, Tai, Viva W, Jones, Grace M, Palii, Sergiu P, Velasco-Alin, Moises, Pan, Karen, Patterson, Bruce W, Gugliucci, Alejandro, Lustig, Robert H, Mulligan, Kathleen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017
• Subjects: Adolescent; African Americans; Child; Dietary Carbohydrates - administration & dosage; Dietary Treatment; Female; Fructose - administration & dosage; Gastroenterology and Hepatology; Glucose Tolerance Test; Hispanic Americans; Humans; Insulin - metabolism; Intra-Abdominal Fat - diagnostic imaging; Lipogenesis; Liver - diagnostic imaging; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Metabolic Syndrome - complications; Metabolic Syndrome - physiopathology; NAFLD; Overweight; Pediatric; Pediatric Obesity - complications; Pediatric Obesity - physiopathology; Subcutaneous Fat - diagnostic imaging; T2DM; milliseconds; NAFLD; magnetic resonance; DNL; non-alcoholic fatty liver disease; oral glucose tolerance test; K 2EDTA; SAT; VAT; alanine aminotransferase; ALT; oral glucose test of insulin sensitivity; de novo lipogenesis; dietary treatment; pediatric; AUC; ANCOVA; L/W; composite insulin sensitivity index; type 2 diabetes mellitus; potassium ethylenediaminetetraacetic acid; subcutaneous adipose tissue; overweight; visceral adipose tissue; BMI; homeostatic model assessment of insulin resistance; cardiovascular disease; CISI; MR; body mass index; ms; OGIS; ISR; area under the curve; DXA; CVD; HOMA-IR; dual-energy X-ray absorptiometry; lipid/water; insulin secretion rate; adenosine triphosphate; OGTT; ATP; analysis of covariance; IQR; Overweight; Dietary Treatment; Pediatric
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2017.05.043

Abstract Background & Aims Consumption of sugar is associated with obesity, type 2 diabetes mellitus, non-alcoholic 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 more than 50 g/day). 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 kcal. 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% (inter-quartile range, 2.5%–14.8%) to 3.8% (inter-quartile range, 1.7%–15.5%)( P <.001) and VAT decreased from 123 cm3 (inter-quartile range, 85–145 cm3 ) to 110 cm3 (inter-quartile range, 84–134 cm3 ) ( P <.001). The DNL area under the curve decreased from 68% (inter-quartile range, 46%–83%) to 26% (inter-quartile range, 16%– 37%) ( P <0.001). Insulin kinetics improved ( P <.001). These changes occurred irrespective of baseline liver fat. Conclusions Short-term (9 day) 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 no: NCT01200043