Vanderbilt Univ. School of Medicine, Nashville, TN 37232, USA.
Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E887-98. doi: 10.1152/ajpendo.00372.2010. Epub 2010 Sep 7.
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.
本研究的目的是评估大型动物模型对高脂肪和果糖饮食（HFFD）的反应。在喂食 HFFD（n=10）或对照饮食（CTR，n=4）13 周期间进行了三种不同的代谢评估：口服葡萄糖耐量试验（OGTT；基线、4 和 8 周）、高胰岛素-正常血糖钳夹（HIEG；基线和 10 周）和高胰岛素-高血糖钳夹（HIHG，13 周）。在 HFFD 喂养 4 周和 8 周后，OGTT 期间葡萄糖的 ΔAUC 增加了一倍以上，在 HIEG 钳夹期间维持正常血糖所需的平均葡萄糖输注率在 HFFD 喂养 10 周后降低了约 30%。这些变化在 CTR 组中没有发生。HIHG 钳夹包括实验期 1（P1，0-90 分钟）和 2（P2，90-180 分钟）。在 P1 期间，输注了生长抑素、基础门静脉胰高血糖素、4×基础门静脉胰岛素和外周葡萄糖（使肝葡萄糖负荷增加一倍）；在 P2 期间，门静脉也输注了葡萄糖（4.0mg·kg(-1)·min(-1)）。在 HFFD 组中，P1 和 P2 期间的净肝葡萄糖摄取量分别为-0.4±0.1[输出]和 0.2±0.8mg·kg(-1)·min(-1)，而在 CTR 组中，P1 和 P2 期间的净肝葡萄糖摄取量分别为 1.8±0.8 和 3.5±1.0mg·kg(-1)·min(-1)（与 HFFD 相比，P<0.05）。HFFD 和 CTR 组的直接途径糖原合成分别为 0.5±0.2 和 1.5±0.4mg·kg(-1)·min(-1)（与 HFFD 相比，P<0.05）。总之，长期摄入 HFFD 会降低肝脏对激素和血糖信号的敏感性，并导致 NHGU 和糖原合成明显受损。
