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, 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 e...

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Veröffentlicht in:Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2017-09, Vol.153 (3), p.743-752
Hauptverfasser: 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
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container_issue 3
container_start_page 743
container_title Gastroenterology (New York, N.Y. 1943)
container_volume 153
creator 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
description 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
doi_str_mv 10.1053/j.gastro.2017.05.043
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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 &lt;.001) and VAT decreased from 123 cm3 (inter-quartile range, 85–145 cm3 ) to 110 cm3 (inter-quartile range, 84–134 cm3 ) ( P &lt;.001). The DNL area under the curve decreased from 68% (inter-quartile range, 46%–83%) to 26% (inter-quartile range, 16%– 37%) ( P &lt;0.001). Insulin kinetics improved ( P &lt;.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</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1053/j.gastro.2017.05.043</identifier><identifier>PMID: 28579536</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; African Americans ; Child ; Dietary Carbohydrates - administration &amp; dosage ; Dietary Treatment ; Female ; Fructose - administration &amp; 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</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 2017-09, Vol.153 (3), p.743-752</ispartof><rights>AGA Institute</rights><rights>2017 AGA Institute</rights><rights>Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-d79bde8c4a0e342630eaf1772311413ac90bcbf5d46489a8c54c2d5a58ae64003</citedby><cites>FETCH-LOGICAL-c518t-d79bde8c4a0e342630eaf1772311413ac90bcbf5d46489a8c54c2d5a58ae64003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0016508517356858$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28579536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schwarz, Jean-Marc</creatorcontrib><creatorcontrib>Noworolski, Susan M</creatorcontrib><creatorcontrib>Erkin-Cakmak, Ayca</creatorcontrib><creatorcontrib>Korn, Natalie J</creatorcontrib><creatorcontrib>Wen, Michael J</creatorcontrib><creatorcontrib>Tai, Viva W</creatorcontrib><creatorcontrib>Jones, Grace M</creatorcontrib><creatorcontrib>Palii, Sergiu P</creatorcontrib><creatorcontrib>Velasco-Alin, Moises</creatorcontrib><creatorcontrib>Pan, Karen</creatorcontrib><creatorcontrib>Patterson, Bruce W</creatorcontrib><creatorcontrib>Gugliucci, Alejandro</creatorcontrib><creatorcontrib>Lustig, Robert H</creatorcontrib><creatorcontrib>Mulligan, Kathleen</creatorcontrib><title>Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children with Obesity</title><title>Gastroenterology (New York, N.Y. 1943)</title><addtitle>Gastroenterology</addtitle><description>Abstract Background &amp; 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 &lt;.001) and VAT decreased from 123 cm3 (inter-quartile range, 85–145 cm3 ) to 110 cm3 (inter-quartile range, 84–134 cm3 ) ( P &lt;.001). The DNL area under the curve decreased from 68% (inter-quartile range, 46%–83%) to 26% (inter-quartile range, 16%– 37%) ( P &lt;0.001). Insulin kinetics improved ( P &lt;.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</description><subject>Adolescent</subject><subject>African Americans</subject><subject>Child</subject><subject>Dietary Carbohydrates - administration &amp; dosage</subject><subject>Dietary Treatment</subject><subject>Female</subject><subject>Fructose - administration &amp; dosage</subject><subject>Gastroenterology and Hepatology</subject><subject>Glucose Tolerance Test</subject><subject>Hispanic Americans</subject><subject>Humans</subject><subject>Insulin - metabolism</subject><subject>Intra-Abdominal Fat - diagnostic imaging</subject><subject>Lipogenesis</subject><subject>Liver - diagnostic imaging</subject><subject>Magnetic Resonance Imaging</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Metabolic Syndrome - complications</subject><subject>Metabolic Syndrome - physiopathology</subject><subject>NAFLD</subject><subject>Overweight</subject><subject>Pediatric</subject><subject>Pediatric Obesity - complications</subject><subject>Pediatric Obesity - physiopathology</subject><subject>Subcutaneous Fat - diagnostic imaging</subject><issn>0016-5085</issn><issn>1528-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1vEzEQhi0EoqHwDxDykUN3sdf2rveChNKmVERU4uNseb2zicPGDrY3kH9fRynl44JkaazxzDueeQahl5SUlAj2ZlOudEzBlxWhTUlESTh7hGZUVLIghFaP0SybuhBEijP0LMYNIaRlkj5FZ5UUTStYPUM_r4YBTIrYD_jSQtLhgBdhMslHwJ8gF7AmWe9wPku7h4AXOl3gS8Af_d5n186vwEG08QJr1-MbF6fROvzBOkjWRJzv87Ud-wAO_7BpjW-7HJ0Oz9GTQY8RXtzbc_R1cfVl_r5Y3l7fzN8tCyOoTEXftF0P0nBNgPGqZgT0QJumYpRyyrRpSWe6QfS85rLV0ghuql5oITXUnBB2jt6edHdTt4XegEtBj2oX7Db3qry26u8XZ9dq5fdKSMoq2WaB1_cCwX-f8kTU1kYD46gd-Ckq2pKaclE3PIfyU6gJPsYAw0MZStQRmtqoEzR1hKaIUBlaTnv15xcfkn5R-t0D5EHtLQQVjQVnoLchw1O9t_-r8K-AyZCs0eM3OEDc-Cm4DEFRFStF1Ofj4hz3hjZM1FJIdgfTM8ES</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Schwarz, Jean-Marc</creator><creator>Noworolski, Susan M</creator><creator>Erkin-Cakmak, Ayca</creator><creator>Korn, Natalie J</creator><creator>Wen, Michael J</creator><creator>Tai, Viva W</creator><creator>Jones, Grace M</creator><creator>Palii, Sergiu P</creator><creator>Velasco-Alin, Moises</creator><creator>Pan, Karen</creator><creator>Patterson, Bruce W</creator><creator>Gugliucci, Alejandro</creator><creator>Lustig, Robert H</creator><creator>Mulligan, Kathleen</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170901</creationdate><title>Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children with Obesity</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-d79bde8c4a0e342630eaf1772311413ac90bcbf5d46489a8c54c2d5a58ae64003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>African Americans</topic><topic>Child</topic><topic>Dietary Carbohydrates - administration &amp; dosage</topic><topic>Dietary Treatment</topic><topic>Female</topic><topic>Fructose - administration &amp; dosage</topic><topic>Gastroenterology and Hepatology</topic><topic>Glucose Tolerance Test</topic><topic>Hispanic Americans</topic><topic>Humans</topic><topic>Insulin - metabolism</topic><topic>Intra-Abdominal Fat - diagnostic imaging</topic><topic>Lipogenesis</topic><topic>Liver - diagnostic imaging</topic><topic>Magnetic Resonance Imaging</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Metabolic Syndrome - complications</topic><topic>Metabolic Syndrome - physiopathology</topic><topic>NAFLD</topic><topic>Overweight</topic><topic>Pediatric</topic><topic>Pediatric Obesity - complications</topic><topic>Pediatric Obesity - physiopathology</topic><topic>Subcutaneous Fat - diagnostic imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schwarz, Jean-Marc</creatorcontrib><creatorcontrib>Noworolski, Susan M</creatorcontrib><creatorcontrib>Erkin-Cakmak, Ayca</creatorcontrib><creatorcontrib>Korn, Natalie J</creatorcontrib><creatorcontrib>Wen, Michael J</creatorcontrib><creatorcontrib>Tai, Viva W</creatorcontrib><creatorcontrib>Jones, Grace M</creatorcontrib><creatorcontrib>Palii, Sergiu P</creatorcontrib><creatorcontrib>Velasco-Alin, Moises</creatorcontrib><creatorcontrib>Pan, Karen</creatorcontrib><creatorcontrib>Patterson, Bruce W</creatorcontrib><creatorcontrib>Gugliucci, Alejandro</creatorcontrib><creatorcontrib>Lustig, Robert H</creatorcontrib><creatorcontrib>Mulligan, Kathleen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schwarz, Jean-Marc</au><au>Noworolski, Susan M</au><au>Erkin-Cakmak, Ayca</au><au>Korn, Natalie J</au><au>Wen, Michael J</au><au>Tai, Viva W</au><au>Jones, Grace M</au><au>Palii, Sergiu P</au><au>Velasco-Alin, Moises</au><au>Pan, Karen</au><au>Patterson, Bruce W</au><au>Gugliucci, Alejandro</au><au>Lustig, Robert H</au><au>Mulligan, Kathleen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children with Obesity</atitle><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle><addtitle>Gastroenterology</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>153</volume><issue>3</issue><spage>743</spage><epage>752</epage><pages>743-752</pages><issn>0016-5085</issn><eissn>1528-0012</eissn><abstract>Abstract Background &amp; 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 &lt;.001) and VAT decreased from 123 cm3 (inter-quartile range, 85–145 cm3 ) to 110 cm3 (inter-quartile range, 84–134 cm3 ) ( P &lt;.001). The DNL area under the curve decreased from 68% (inter-quartile range, 46%–83%) to 26% (inter-quartile range, 16%– 37%) ( P &lt;0.001). Insulin kinetics improved ( P &lt;.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</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28579536</pmid><doi>10.1053/j.gastro.2017.05.043</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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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
title Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children with Obesity
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