BACKGROUND: Controversy exists regarding the causative role of dietary fructose in obesity and fatty liver diseases. Clinical trials have indicated that negative health consequences may occur only when fructose is consumed within excess calories. Animal studies have suggested that fructose impairs intestinal integrity and leads to hepatic steatosis (HS). OBJECTIVES: We assessed nonhuman primates after chronic ad libitum and short-term calorically controlled consumption of a high-fructose (HFr), low-fat diet (24% of calories). Microbial translocation (MT), microbiome, and metabolic health indexes were evaluated. DESIGN: Seventeen monkeys fed 0.3–7 y of an HFr ad libitum diet were compared with 10 monkeys fed a low-fructose, low-fat diet (control). Ten middle-aged, weight-stable, fructose-naive monkeys were stratified into HFr and control groups fed for 6 wk at caloric amounts required to maintain weight stability. Metabolic endpoints, feces, liver, small and large intestinal biopsies, and portal blood samples were collected. RESULTS: Monkeys allowed ad libitum HFr developed HS in contrast to the control diet, and the extent of ectopic fat was related to the duration of feeding. Diabetes incidence also increased. Monkeys that consumed calorically controlled HFr showed significant increases in biomarkers of liver damage, endotoxemia, and MT indexes and a trend for greater hepatitis that was related to MT; however, HS did not develop. CONCLUSIONS: Even in the absence of weight gain, fructose rapidly causes liver damage that we suggest is secondary to endotoxemia and MT. HS relates to the duration of fructose consumption and total calories consumed. These data support fructose inducing both MT and ectopic fat deposition in primates.
BACKGROUND: Controversy exists regarding the causative role of dietary fructose in obesity and fatty liver diseases. Clinical trials have indicated that negative health consequences may occur only when fructose is consumed within excess calories. Animal studies have suggested that fructose impairs intestinal integrity and leads to hepatic steatosis (HS). OBJECTIVES: We assessed nonhuman primates after chronic ad libitum and short-term calorically controlled consumption of a high-fructose (HFr), low-fat diet (24% of calories). Microbial translocation (MT), microbiome, and metabolic health indexes were evaluated. DESIGN: Seventeen monkeys fed 0.3–7 y of an HFr ad libitum diet were compared with 10 monkeys fed a low-fructose, low-fat diet (control). Ten middle-aged, weight-stable, fructose-naive monkeys were stratified into HFr and control groups fed for 6 wk at caloric amounts required to maintain weight stability. Metabolic endpoints, feces, liver, small and large intestinal biopsies, and portal blood samples were collected. RESULTS: Monkeys allowed ad libitum HFr developed HS in contrast to the control diet, and the extent of ectopic fat was related to the duration of feeding. Diabetes incidence also increased. Monkeys that consumed calorically controlled HFr showed significant increases in biomarkers of liver damage, endotoxemia, and MT indexes and a trend for greater hepatitis that was related to MT; however, HS did not develop. CONCLUSIONS: Even in the absence of weight gain, fructose rapidly causes liver damage that we suggest is secondary to endotoxemia and MT. HS relates to the duration of fructose consumption and total calories consumed. These data support fructose inducing both MT and ectopic fat deposition in primates.
Authors: Andrew A Bremer; Kimber L Stanhope; James L Graham; Bethany P Cummings; Wenli Wang; Benjamin R Saville; Peter J Havel Journal: Clin Transl Sci Date: 2011-08 Impact factor: 4.689
Authors: Katie Colbert Coate; Melanie Scott; Ben Farmer; Mary Courtney Moore; Marta Smith; Joshua Roop; Doss W Neal; Phil Williams; Alan D Cherrington Journal: Am J Physiol Endocrinol Metab Date: 2010-09-07 Impact factor: 4.310
Authors: John L Sievenpiper; Russell J de Souza; Arash Mirrahimi; Matthew E Yu; Amanda J Carleton; Joseph Beyene; Laura Chiavaroli; Marco Di Buono; Alexandra L Jenkins; Lawrence A Leiter; Thomas M S Wolever; Cyril W C Kendall; David J A Jenkins Journal: Ann Intern Med Date: 2012-02-21 Impact factor: 25.391
Authors: Earl S Ford; Matthias B Schulze; Manuela M Bergmann; Claus Thamer; Hans-Georg Joost; Heiner Boeing Journal: Diabetes Care Date: 2008-03-17 Impact factor: 19.112
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: Jacques Amar; Rémy Burcelin; Jean Bernard Ruidavets; Patrice D Cani; Josette Fauvel; Marie Christine Alessi; Bernard Chamontin; Jean Ferriéres Journal: Am J Clin Nutr Date: 2008-05 Impact factor: 7.045
Authors: Kylie Kavanagh; Ashley T Wylie; Kelly L Tucker; Timothy J Hamp; Raad Z Gharaibeh; Anthony A Fodor; John M Cullen Journal: Am J Clin Nutr Date: 2013-11 Impact factor: 7.045
Authors: Jessica N Kuzma; Gail Cromer; Derek K Hagman; Kara L Breymeyer; Christian L Roth; Karen E Foster-Schubert; Sarah E Holte; David S Weigle; Mario Kratz Journal: Am J Clin Nutr Date: 2016-06-29 Impact factor: 7.045
Authors: E L Mitchell; A T Davis; K Brass; M Dendinger; R Barner; R Gharaibeh; A A Fodor; K Kavanagh Journal: J Nutr Health Aging Date: 2017 Impact factor: 4.075
Authors: Aslihan Yerlikaya; Tuncay Dagel; Christopher King; Masanari Kuwabara; Miguel A Lanaspa; Ana Andres-Hernando; Adrian Covic; Jacek Manitius; Alan A Sag; Mehmet Kanbay Journal: Int Urol Nephrol Date: 2017-02-16 Impact factor: 2.370
Authors: Jelena Todoric; Giuseppe Di Caro; Saskia Reibe; Darren C Henstridge; Courtney R Green; Alison Vrbanac; Fatih Ceteci; Claire Conche; Reginald McNulty; Shabnam Shalapour; Koji Taniguchi; Peter J Meikle; Jeramie D Watrous; Rafael Moranchel; Mahan Najhawan; Mohit Jain; Xiao Liu; Tatiana Kisseleva; Maria T Diaz-Meco; Jorge Moscat; Rob Knight; Florian R Greten; Lester F Lau; Christian M Metallo; Mark A Febbraio; Michael Karin Journal: Nat Metab Date: 2020-08-24