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Chronic consumption of a high-fat/high-fructose diet renders the liver incapable of net hepatic glucose uptake.

Coate KC, Scott M, Farmer B, Moore MC, Smith M, Roop J, Neal DW, Williams P, Cherrington AD
Am J Physiol Endocrinol Metab. 2010 299 (6): E887-98

PMID: 20823448 · PMCID: PMC3006253 · DOI:10.1152/ajpendo.00372.2010

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.

MeSH Terms (15)

Analysis of Variance Animals Area Under Curve Biological Transport Dietary Carbohydrates Dietary Fats Dogs Fructose Glucagon Glucose Glucose Clamp Technique Glucose Intolerance Glucose Tolerance Test Liver Male

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