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Open AccessArticle

Dietary Leucine Supplement Ameliorates Hepatic Steatosis and Diabetic Nephropathy in db/db Mice

1
Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taoyuan 333, Taiwan
2
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
3
Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan
4
Metabolomics Core Laboratory, Chang Gung University, Taoyuan 333, Taiwan
5
Clinical Phenome Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
6
Department of Physiology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(7), 1921; https://doi.org/10.3390/ijms19071921
Received: 31 May 2018 / Revised: 25 June 2018 / Accepted: 29 June 2018 / Published: 30 June 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
Dietary leucine supplementation has been explored for the therapeutic intervention of obesity and obesity-induced metabolic dysfunctions. In this study, we aim to examine the effects of dietary leucine supplementation in db/db mice. Mice were treated with or without leucine (1.5% w/v) in drinking water for 12 weeks. The leucine supplement was found to reduce insulin resistance and hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based lipidomics, we found that the reduction of hepatic triglyceride synthesis was correlated with attenuated development of fatty liver. In addition, diabetic nephropathy (DN) was also ameliorated by leucine. Using liquid chromatography–time-of-flight mass spectrometry (LC-TOF MS)-based urine metabolomics analysis, we found that the disturbance of the tricarboxylic acid (TCA) cycle was reversed by leucine. The beneficial effects of leucine were probably due to AMP-activated protein kinase (AMPK) activation in the liver and kidneys of db/db mice. Thus, dietary leucine supplementation may potentially be a nutritional intervention to attenuate hepatic steatosis and early DN in type II diabetes. View Full-Text
Keywords: leucine; hepatic steatosis; diabetic nephropathy; db/db mice; metabolomics leucine; hepatic steatosis; diabetic nephropathy; db/db mice; metabolomics
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Chen, K.-H.; Chen, Y.-L.; Tang, H.-Y.; Hung, C.-C.; Yen, T.-H.; Cheng, M.-L.; Shiao, M.-S.; Chen, J.-K. Dietary Leucine Supplement Ameliorates Hepatic Steatosis and Diabetic Nephropathy in db/db Mice. Int. J. Mol. Sci. 2018, 19, 1921.

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