Abstract
The available findings concerning the association between branched-chain amino acids (BCAAs)—particularly leucine—and insulin resistance are conflicting. BCAAs have been proposed to elicit different or even opposite effects, depending on the prevalence of catabolic and anabolic states. We tested the hypothesis that leucine supplementation may exert different effects at different stages of insulin resistance, to provide mechanistic insights into the role of leucine in the progression of insulin resistance. Male Sprague-Dawley rats were fed a normal chow diet, high-fat diet (HFD), HFD supplemented with 1.5% leucine, or HFD with a 20% calorie restriction for 24 or 32 weeks. Leucine supplementation led to abnormal catabolism of BCAA and the incompletely oxidized lipid species that contributed to mitochondrial dysfunction in skeletal muscle in HFD-fed rats in the early stage of insulin resistance (24 weeks). However, leucine supplementation induced no remarkable alternations in BCAA catabolism, but did enhance mitochondrial biogenesis with a concomitant improvement in lipid oxidation and mitochondrial function during the hyperglycaemia stage (32 weeks). These findings suggest that leucine trigger different effects on metabolic signatures at different stages of insulin resistance, and the overall metabolic status of the organisms should be carefully considered to potentiate the benefits of leucine.
Highlights
Branched-chain amino acids (BCAAs), comprising leucine, isoleucine and valine, are essential amino acids and important nutrient signals that have direct and indirect effects on metabolism.Substantial evidence indicates that increased dietary intake of branched-chain amino acids (BCAAs), leucine, has positive effects on the regulation of body weight, muscle protein synthesis, glucose homeostasis, lipid metabolism, and the ageing process [1,2,3,4]
high-fat diet (HFD)-induced weight gain was significantly attenuated by calorie restriction (CR) or leucine supplementation from 3 or 13 weeks, respectively
Newgard et al suggested that excess BCAAs could contribute to development of insulin resistance, at least under conditions of high fat feeding or elevated tissue fatty acid availability [7]
Summary
Branched-chain amino acids (BCAAs), comprising leucine, isoleucine and valine, are essential amino acids and important nutrient signals that have direct and indirect effects on metabolism.Substantial evidence indicates that increased dietary intake of BCAAs, leucine, has positive effects on the regulation of body weight, muscle protein synthesis, glucose homeostasis, lipid metabolism, and the ageing process [1,2,3,4]. Leucine supplementation has no effect, or leads to deterioration in insulin sensitivity [5,6] Along with these effects on metabolic health, it has long been recognized that elevated levels of Nutrients 2017, 9, 565; doi:10.3390/nu9060565 www.mdpi.com/journal/nutrients. Nutrients 2017, 9, 565 circulating BCAAs and related metabolites are strongly associated with obesity and insulin resistance and are predictive of future type 2 diabetes mellitus (T2DM) in humans and in some rodent models [7,8,9,10]. The mechanisms underlying these paradoxical findings are not completely understood
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