Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin-target tissues
Version of Record online: 13 FEB 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Cocoa and Human Health
Volume 57, Issue 6, pages 1067–1079, June 2013
How to Cite
Li, X., Wang, X., Liu, R., Ma, Y., Guo, H., Hao, L., Yao, P., Liu, L., Sun, X., He, K., Cao, W. and Yang, X. (2013), Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin-target tissues. Mol. Nutr. Food Res., 57: 1067–1079. doi: 10.1002/mnfr.201200311
- Issue online: 7 JUN 2013
- Version of Record online: 13 FEB 2013
- Manuscript Accepted: 29 DEC 2012
- Manuscript Revised: 2 DEC 2012
- Manuscript Received: 23 MAY 2012
- National Natural Science Foundation of China (NSFC). Grant Number: 30800907
- Fundamental Research Funds for the Central Universities. Grant Number: 2011TS055
- Wuhan Programs for Science and Technology Development. Grant Number: 200852199599
- Hubei Provincial Department of Health Talent Fund. Grant Number: QJX2008–52
- Insulin resistance;
- Insulin signaling;
This study investigated the effect of chronic leucine supplementation on insulin sensitivity and the associated mechanisms in rats on high-fat diet (HFD).
Methods and results
Male Sprague–Dawley rats were fed either normal chow diet or HFD supplemented with 0, 1.5, 3.0, and 4.5% leucine for 24 weeks. We found that chronic leucine supplementation increased insulin sensitivity together with increased body weight in rats on HFD, but had no effect on insulin sensitivity in rats on normal chow diet. The increased insulin sensitivity by leucine supplementation was not associated with altered ectopic fat accumulation in liver and muscle, plasma levels of lipids and cytokines, but is associated with reduced oxidative stress and improved insulin signaling. Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues.
Chronic leucine supplementation can increase insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in rats on HFD.