Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men
Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men
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DOI：
10.1113/jphysiol.2009.169078
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发表时间：
2009-05-15
影响因子：
5.5
通讯作者：
Vaag, Allan
中科院分区：
文献类型：
--
作者：
Brons, Charlotte;Jensen, Christine B.;Vaag, Allan
高脂肪、高热量饮食与肥胖和2型糖尿病有关。然而，代谢缺陷对高血糖症和2型糖尿病的发展的相对贡献是有争议的。在胰岛素抵抗和2型糖尿病中，肌肉和脂肪组织中过量脂肪的积累可能与线粒体氧化磷酸化缺陷有关。本研究的目的是调查短期脂肪过度喂养对年轻男性葡萄糖和胰岛素代谢的急性影响。我们研究了5天的高脂肪（60%的能量）过度喂养（+50%）与对照饮食对肝脏和外周胰岛素作用的影响，通过高胰岛素正常血钳夹，通过P-31磁共振波谱分析，并通过qrt-PCR和微阵列在26名年轻男性中的基因表达。肝脏葡萄糖生成和空腹血糖水平显着增加，以响应过度喂养。然而，外周胰岛素的作用，肌肉线粒体功能，一般和特定的氧化磷酸化基因的表达不受高脂喂养。胰岛素分泌适当增加以补偿肝脏而非外周胰岛素抵抗。高脂喂养增加空腹血浆脂联素、瘦素和抑胃肽（GIP）水平。高脂肪过量喂养会增加空腹血糖水平，这是由于肝脏葡萄糖生成增加。增加的胰岛素分泌可以补偿可能由升高的GIP分泌介导的肝胰岛素抵抗。胰岛素分泌增加先于外周胰岛素抵抗、线粒体功能障碍和肥胖症的发展，提示胰岛素本身以及GIP在外周胰岛素抵抗和肥胖症的发展中的作用。
A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2 diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days' high-fat (60% energy) overfeeding (+50%) versus a control diet on hepatic and peripheral insulin action by a hyperinsulinaemic euglycaemic clamp, muscle mitochondrial function by P-31 magnetic resonance spectroscopy, and gene expression by qrt-PCR and microarray in 26 young men. Hepatic glucose production and fasting glucose levels increased significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral, insulin resistance. High-fat feeding increased fasting levels of plasma adiponectin, leptin and gastric inhibitory peptide (GIP). High-fat overfeeding increases fasting glucose levels due to increased hepatic glucose production. The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion. Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the development of peripheral insulin resistance and obesity.