Jean-Marc Schwarz1, Susan M Noworolski2, Ayca Erkin-Cakmak3, Natalie J Korn2, Michael J Wen4, Viva W Tai5, Grace M Jones6, Sergiu P Palii6, Moises Velasco-Alin7, Karen Pan4, Bruce W Patterson8, Alejandro Gugliucci6, Robert H Lustig3, Kathleen Mulligan7. 1. Touro University California College of Osteopathic Medicine, Vallejo, California; Department of Medicine, Division of Endocrinology, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California. Electronic address: Jean-Marc.Schwarz@tu.edu. 2. Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California. 3. Department of Pediatrics, University of California, San Francisco, Benioff Children's Hospital, San Francisco, California. 4. Department of Medicine, Division of Endocrinology, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California. 5. Clinical and Translational Science Institute Clinical Research Service, University of California, San Francisco, San Francisco, California. 6. Touro University California College of Osteopathic Medicine, Vallejo, California. 7. Touro University California College of Osteopathic Medicine, Vallejo, California; Department of Medicine, Division of Endocrinology, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California. 8. Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri.
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.
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.
Authors: Kerry L Donnelly; Coleman I Smith; Sarah J Schwarzenberg; Jose Jessurun; Mark D Boldt; Elizabeth J Parks Journal: J Clin Invest Date: 2005-05 Impact factor: 14.808
Authors: J M Schwarz; R Chioléro; J P Revelly; C Cayeux; P Schneiter; E Jéquier; T Chen; L Tappy Journal: Am J Clin Nutr Date: 2000-10 Impact factor: 7.045
Authors: Jean-Marc Schwarz; Kathleen Mulligan; Jeongae Lee; Joan C Lo; Michael Wen; Mustafa A Noor; Carl Grunfeld; Morris Schambelan Journal: J Clin Endocrinol Metab Date: 2002-02 Impact factor: 5.958
Authors: Elisa Fabbrini; Faidon Magkos; B Selma Mohammed; Terri Pietka; Nada A Abumrad; Bruce W Patterson; Adewole Okunade; Samuel Klein Journal: Proc Natl Acad Sci U S A Date: 2009-08-24 Impact factor: 11.205
Authors: Thomas Jensen; Manal F Abdelmalek; Shelby Sullivan; Kristen J Nadeau; Melanie Green; Carlos Roncal; Takahiko Nakagawa; Masanari Kuwabara; Yuka Sato; Duk-Hee Kang; Dean R Tolan; Laura G Sanchez-Lozada; Hugo R Rosen; Miguel A Lanaspa; Anna Mae Diehl; Richard J Johnson Journal: J Hepatol Date: 2018-02-02 Impact factor: 25.083
Authors: Laura G Sanchez-Lozada; Ana Andres-Hernando; Fernando E Garcia-Arroyo; Christina Cicerchi; Nanxing Li; Masanari Kuwabara; Carlos A Roncal-Jimenez; Richard J Johnson; Miguel A Lanaspa Journal: J Biol Chem Date: 2019-01-16 Impact factor: 5.157
Authors: Grace Marie Jones; Russell Caccavello; Sergiu P Palii; Clive R Pullinger; John P Kane; Kathleen Mulligan; Alejandro Gugliucci; Jean-Marc Schwarz Journal: J Lipid Res Date: 2019-12-30 Impact factor: 5.922