Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates.

TitleDietary fructose induces endotoxemia and hepatic injury in calorically controlled primates.
Publication TypeJournal Article
Year of Publication2013
AuthorsKavanagh K, Wylie AT, Tucker KL, Hamp TJ, Gharaibeh RZ, Fodor AA, Cullen JMCullen
JournalAm J Clin Nutr
Volume98
Issue2
Pagination349-57
Date Published2013 Aug
ISSN1938-3207
KeywordsAnimal Feed, Animals, Diet, Fat-Restricted, Endotoxemia, Endpoint Determination, Energy Intake, Fatty Liver, Female, Fructose, Haplorhini, Liver, Male, Metagenome, Obesity, Weight Gain
Abstract

<p><b>BACKGROUND: </b>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).</p><p><b>OBJECTIVES: </b>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.</p><p><b>DESIGN: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>

DOI10.3945/ajcn.112.057331
Alternate JournalAm. J. Clin. Nutr.
PubMed ID23783298
PubMed Central IDPMC3712547
Grant ListK01AG 033641 / AG / NIA NIH HHS / United States
OD010965 / OD / NIH HHS / United States
RR019963 / RR / NCRR NIH HHS / United States