title: Chronic consumption of a high-fat/high-fructose diet renders the liver incapable of net hepatic glucose uptake.
abstract: The objective of this study was to assess the response of a large animal model to high dietary fat and fructose (HFFD). Three different metabolic assessments were performed during 13 wk of feeding an HFFD (n = 10) or chow control (CTR, n = 4) diet: oral glucose tolerance tests (OGTTs; baseline, 4 and 8 wk), hyperinsulinemic-euglycemic clamps (HIEGs; baseline and 10 wk) and hyperinsulinemic-hyperglycemic clamps (HIHGs, 13 wk). The ΔAUC for glucose during the OGTTs more than doubled after 4 and 8 wk of HFFD feeding, and the average glucose infusion rate required to maintain euglycemia during the HIEG clamps decreased by ≈30% after 10 wk of HFFD feeding. These changes did not occur in the CTR group. The HIHG clamps included experimental periods 1 (P1, 0-90 min) and 2 (P2, 90-180 min). During P1, somatostatin, basal intraportal glucagon, 4 × basal intraportal insulin, and peripheral glucose (to double the hepatic glucose load) were infused; during P2, glucose was also infused intraportally (4.0 mg·kg(-1)·min(-1)). Net hepatic glucose uptake during P1 and P2 was -0.4 ± 0.1 [output] and 0.2 ± 0.8 mg·kg(-1)·min(-1) in the HFFD group, respectively, and 1.8 ± 0.8 and 3.5 ± 1.0 mg·kg(-1)·min(-1) in the CTR group, respectively (P < 0.05 vs. HFFD during P1 and P2). Glycogen synthesis through the direct pathway was 0.5 ± 0.2 and 1.5 ± 0.4 mg·kg(-1)·min(-1) in the HFFD and CTR groups, respectively (P < 0.05 vs. HFFD). In conclusion, chronic consumption of an HFFD diminished the sensitivity of the liver to hormonal and glycemic cues and resulted in a marked impairment in NHGU and glycogen synthesis.
authors.affiliation: Vanderbilt Univ. School of Medicine, Nashville, TN 37232, USA. katie.colbert@vanderbilt.edu
authors.forename: Katie Colbert
authors.initials: KC
authors.lastname: Coate
authors.forename: Melanie
authors.initials: M
authors.lastname: Scott
authors.forename: Ben
authors.initials: B
authors.lastname: Farmer
authors.forename: Mary Courtney
authors.initials: MC
authors.lastname: Moore
authors.forename: Marta
authors.initials: M
authors.lastname: Smith
authors.forename: Joshua
authors.initials: J
authors.lastname: Roop
authors.forename: Doss W
authors.initials: DW
authors.lastname: Neal
authors.forename: Phil
authors.initials: P
authors.lastname: Williams
authors.forename: Alan D
authors.initials: AD
authors.lastname: Cherrington
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001692:Biological Transport; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D004285:Dogs; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000209:etiology / Q000378:metabolism*; D005951:Glucose Tolerance Test; D008099:Liver / Q000378:metabolism*; D008297:Male
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005632:Fructose; D005934:Glucagon; D005947:Glucose
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