Training in the fasted state improves glucose tolerance during fat-rich diet

Abstract

A fat-rich energy-dense diet is an important cause of insulin resistance. Stimulation of fat turnover in muscle cells during dietary fat challenge may contribute to maintenance of insulin sensitivity. Exercise in the fasted state markedly stimulates energy provision via fat oxidation. Therefore, we investigated whether exercise training in the fasted state is more potent than exercise in the fed state to rescue whole-body glucose tolerance and insulin sensitivity during a period of hyper-caloric fat-rich diet. Healthy male volunteers (18-25 y) received a hyper-caloric (∼+30% kcal day(-1)) fat-rich (50% of kcal) diet for 6 weeks. Some of the subjects performed endurance exercise training (4 days per week) in the fasted state (F; n = 10), whilst the others ingested carbohydrates before and during the training sessions (CHO; n = 10). The control group did not train (CON; n = 7). Body weight increased in CON (+3.0 ± 0.8 kg) and CHO (+1.4 ± 0.4 kg) (P < 0.01), but not in F (+0.7 ± 0.4 kg, P = 0.13). Compared with CON, F but not CHO enhanced whole-body glucose tolerance and the Matsuda insulin sensitivity index (P < 0.05). Muscle GLUT4 protein content was increased in F (+28%) compared with both CHO (P = 0.05) and CON (P < 0.05). Furthermore, only training in F elevated AMP-activated protein kinase α phosphorylation (+25%) as well as up-regulated fatty acid translocase/CD36 and carnitine palmitoyltransferase 1 mRNA levels compared with CON (∼+30%). High-fat diet increased intramyocellular lipid but not diacylglycerol and ceramide contents, either in the absence or presence of training. This study for the first time shows that fasted training is more potent than fed training to facilitate adaptations in muscle and to improve whole-body glucose tolerance and insulin sensitivity during hyper-caloric fat-rich diet.

Figures

Figure 1. Effect of high-fat diet, alone or in conjunction with training in either the fasted or the carbohydrate-fed state, on glucose tolerance

Data provided are means ±s.e.m. (CON: n = 7; F: n = 9; CHO: n = 8–9) and represent blood glucose concentrations during a 120 min OGTT. Inset tables show the corresponding serum insulin concentrations (μU ml−1) at 0, 60 and 120 min. Values before (pretest) and after (posttest) a 6-week hyper-caloric fat-rich diet, in either the absence (CON, panel A) or the presence of training in either the fasted state (F, panel B) or the carbohydrate-fed state (CHO, panel C) are shown. Three-way ANOVA was performed to examine the main effects of treatment, time (pretest versus posttest) and time within the OGTT. One outlier (CHO subject) is omitted from the glucose data analysis. *P < 0.05, versus pretest; ‡P = 0.05, versus pretest; IIP = 0.07, versus pretest; §P < 0.05, versus CON pretest; †P < 0.05, versus CON posttest.

Figure 2. Effect of high-fat diet, alone or in conjunction with training in either the fasted or the carbohydrate-fed state, on individual responses on glucose tolerance

Data provided are individual values (CON: n = 7; F: n = 9; CHO: n = 8) and represent area under the glucose curve (AUCgluc) during a 120 min OGTT. Values before (pretest) and after (posttest) a 6-week hyper-caloric fat-rich diet, in either the absence (CON) or the presence of training in either the fasted state (F) or the carbohydrate-fed state (CHO) are shown. One outlier (CHO subject) is omitted from the glucose data analysis.

Figure 3. Effect of high-fat diet, alone or in conjunction with training in either the fasted or the carbohydrate-fed state, on whole-body insulin sensitivity

Data provided are means ±s.e.m. (CON: n = 7; F: n = 9; CHO: n = 9) and represent Matsuda insulin sensitivity index (ISI) as calculated by fasting glucose and insulin values. Values before (pretest) and after (posttest) a 6-week hyper-caloric fat-rich diet, either in the absence (CON) or presence of training in either the fasted state or the carbohydrate-fed state (CHO) are shown. *P < 0.05, versus pretest.

Figure 4. Effect of high-fat diet, alone or in conjunction with training in either the fasted or the carbohydrate-fed state, on muscle total GLUT4 protein content and AMPKα phosphorylation status

Data provided are means ±s.e.m. (CON: n = 7; F: n = 9; CHO: n = 10) and represent total GLUT4 protein content relative to GAPDH (panel A) and AMPKα phosphorylation status relative to total protein content (panel B) in m. vastus lateralis measured by Western blotting. Values before (pretest) and after (posttest) a 6-week hyper-caloric fat-rich diet, in either the absence (CON, open bars) or the presence of training in either the fasted state (F, filled bars) or the carbohydrate-fed state (CHO, hatched bars) are shown. Pretest values in CON were assigned the arbitrary value of 1.0 and all other samples were expressed relative to this value. *P < 0.05, versus pretest.

Figure 5. Effect of high-fat diet, alone or in conjunction with training in either the fasted or the carbohydrate-fed state, on intramyocellular lipid content

Data provided are means ±s.e.m. (CON: n = 7; F: n = 10; CHO: n = 10) and represent basal IMCL content in type I (panel A) and type IIa (panel B) fibres as determined by fluorescence microscopy on Oil-Red-O stained muscle cross-sections (arbitrary units). Values before (pretest) and after (posttest) a 6-week hyper-caloric fat-rich diet, in either the absence (CON, open bars) or the presence of training in either the fasted state (F, filled bars) or the carbohydrate-fed state (CHO, hatched bars) are shown. *P < 0.05, versus pretest; ‡P = 0.06, versus pretest; IIP = 0.09, versus pretest.

Figure 6. Effect of high-fat diet, alone or in conjunction with training in either the fasted or the carbohydrate-fed state, on muscle mRNA content of FAT/CD36 and CPT1

Data provided are means ±s.e.m. (CON: n = 7; F: n = 9; CHO: n = 9) and represent mRNA content of FAT/CD36 (panel A) and CPT1 (panel B) measured by quantitative real time PCR. Values before (pretest) and after (posttest) a 6-week hyper-caloric fat-rich diet, in either the absence (CON, open bars) or the presence of training in either the fasted state (F, filled bars) or the carbohydrate-fed state (CHO, hatched bars) are shown. Pretest values in CON were assigned the arbitrary value of 1.0 and all other samples were expressed relative to this value. *P < 0.05, versus pretest; †P < 0.05, versus CON posttest.