title: Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates.
abstract: 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).
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Pathology Section on Comparative Medicine and Lipid Sciences, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27127, USA. kkavanag@wakehealth.edu
authors.forename: Kylie
authors.initials: K
authors.lastname: Kavanagh
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Wylie
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Tucker
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hamp
authors.forename: Raad Z
authors.initials: RZ
authors.lastname: Gharaibeh
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fodor
authors.forename: John M Cullen
authors.initials: JM
authors.lastname: Cullen
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D018752:Diet, Fat-Restricted; D019446:Endotoxemia / Q000139:chemically induced* / Q000473:pathology; D023381:Endpoint Determination; D002149:Energy Intake; D005234:Fatty Liver / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005632:Fructose / Q000009:adverse effects*; D000882:Haplorhini; D008099:Liver / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D008297:Male; D054892:Metagenome; D009765:Obesity / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D005632:Fructose