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Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men
Article first published online: 14 MAY 2009
© 2009 The Authors. Journal compilation © 2009 The Physiological Society
The Journal of Physiology
Volume 587, Issue 10, pages 2387–2397, May 2009
How to Cite
Brøns, C., Jensen, C. B., Storgaard, H., Hiscock, N. J., White, A., Appel, J. S., Jacobsen, S., Nilsson, E., Larsen, C. M., Astrup, A., Quistorff, B. and Vaag, A. (2009), Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men. The Journal of Physiology, 587: 2387–2397. doi: 10.1113/jphysiol.2009.169078
- Issue published online: 14 MAY 2009
- Article first published online: 14 MAY 2009
- (Received 13 January 2009; accepted after revision 25 March 2009; first published online 30 March 2009)
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 31P 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.