Effects of leucine supplementation and resistance exercise on dexamethasone-induced muscle atrophy and insulin resistance in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: We aimed to evaluate the effects of resistance exercise (RE) and leucine (LEU) supplementation on dexamethasone (DEXA)-induced muscle atrophy and insulin resistance.Methods: Male Wistar rats were randomly divided into DEXA(DEX), DEXA + RE (DEX-RE), DEXA + LEU (DEX-LEU), and DEXA + RE + LEU (DEX-RE-LEU) groups. Each group received DEXA 5 mg . kg(-1) . d(-1) for 7 d from drinking water and were pair-fed to the DEX group; LEU-supplemented groups received 0.135 g . kg(-1) . d(-1) through gavage for 7 d; the RE protocol was based on three sessions of squat-type exercise composed by three sets of 10 repetitions at 70% of maximal voluntary strength capacity.Results: the plantaris mass was significantly greater in both trained groups compared with the non-trained groups. Muscle cross-sectional area and fiber areas did not differ between groups. Both trained groups displayed significant increases in the number of intermediated fibers (IIa/IIx), a decreased number of fast-twitch fibers (IIb), an increased ratio of the proteins phospho(Ser2448)/ total mammalian target of rapamycin and phospho(Thr389)/total 70-kDa ribosomal protein S6 kinase. and a decreased ratio of phospho(Ser253)/total Forkhead box protein-3a. Plasma glucose was significantly increased in the DEX-LEU group compared with the DEX group and RE significantly decreased hyperglycemia. the DEX-LEU group displayed decreased glucose transporter-4 translocation compared with the DEX group and RE restored this response. LEU supplementation worsened insulin sensitivity and did not attenuate muscle wasting in rats treated with DEXA. Conversely, RE modulated glucose homeostasis and fiber type transition in the plantaris muscle.Conclusion: Resistance exercise but not LEU supplementation promoted fiber type transition and improved glucose homeostasis in DEXA-treated rats. (C) 2012 Elsevier Inc. All rights reserved. Univ São Paulo, Lab Appl Nutr & Metab, Sch Phys Educ & Sports, São Paulo, Brazil Univ São Paulo, Inst Biomed Sci, São Paulo, Brazil Univ São Paulo, Lab Mol & Cellular Physiol Exercise, Sch Phys Educ & Sports, São Paulo, Brazil Univ São Paulo, Sch Med, Lab Expt Hypertens, São Paulo, Brazil Universidade Federal de São Paulo, Dept Biosci, São Paulo, Brazil Clermont Univ, UFR Med, UMR Nutr Humaine 1019, Clermont Ferrand, France INRA, UMR Unite Nutr Humaine 1019, F-63122 St Genes Champanelle, France Universidade Federal de São Paulo, Dept Biosci, São Paulo, Brazil FAPESP: 08/51090-1 FAPESP: 10/07062-3 FAPESP: 10/10852-6 FAPESP: 11/04690-6 Web of Science