Dietary fat oxidation is elevated in middle-aged type 2 diabetes

This is the author accepted manuscript. The final version is available from the publisher via the link in this record.N/

Fish oil omega-3 fatty acids partially prevent lipid-induced insulin resistance in human skeletal muscle without limiting acylcarnitine accumulation

This is the author accepted manuscript. The final version is available from Portland Press via the DOI in this record Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil n3PUFA (omega-3 polyunsaturated fatty acids) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that the addition of n3PUFA to an intravenous lipid emulsion would limit muscle acylcarnitine accumulation and reduce the inhibitory effect of lipid overload on insulin action. On three occasions, six healthy young men underwent a 6-h euglycaemic-hyperinsulinaemic clamp accompanied by intravenous infusion of saline (Control), 10% Intralipid® [n6PUFA (omega-6 polyunsaturated fatty acids)] or 10% Intralipid®+10% Omegaven® (2:1; n3PUFA). The decline in insulin-stimulated whole-body glucose infusion rate, muscle PDCa (pyruvate dehydrogenase complex activation) and glycogen storage associated with n6PUFA compared with Control was prevented with n3PUFA. Muscle acetyl-CoA accumulation was greater following n6PUFA compared with Control and n3PUFA, suggesting that mitochondrial lipid overload was responsible for the lower insulin action observed. Despite these favourable metabolic effects of n3PUFA, accumulation of total muscle acylcarnitine was not attenuated when compared with n6PUFA. These findings demonstrate that n3PUFA exert beneficial effects on insulin-stimulated skeletal muscle glucose storage and oxidation independently of total acylcarnitine accumulation, which does not always reflect mitochondrial lipid overload.This research study was funded by The Royal Society [Grant RG100575]

Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use

Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type-specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 ± 4% of maximal O2 uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg−1 h−1) or without (CON placebo trial; water only). Continuous infusions with [U-13C] palmitate and [6,6-2H2] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber-type-specific IMTG and glycogen content. Plasma glucose rate of appearance (Ra) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 ± 19 and 57 ± 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA Ra and subsequent plasma FFA concentrations were lower, resulting in a 34 ± 12% reduction in plasma FFA oxidation rates during exercise (P < 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 ± 21 and 78 ± 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men

Metabolic Factors Limiting Performance in Marathon Runners

Each year in the past three decades has seen hundreds of thousands of runners register to run a major marathon. Of those who attempt to race over the marathon distance of 26 miles and 385 yards (42.195 kilometers), more than two-fifths experience severe and performance-limiting depletion of physiologic carbohydrate reserves (a phenomenon known as ‘hitting the wall’), and thousands drop out before reaching the finish lines (approximately 1–2% of those who start). Analyses of endurance physiology have often either used coarse approximations to suggest that human glycogen reserves are insufficient to fuel a marathon (making ‘hitting the wall’ seem inevitable), or implied that maximal glycogen loading is required in order to complete a marathon without ‘hitting the wall.’ The present computational study demonstrates that the energetic constraints on endurance runners are more subtle, and depend on several physiologic variables including the muscle mass distribution, liver and muscle glycogen densities, and running speed (exercise intensity as a fraction of aerobic capacity) of individual runners, in personalized but nevertheless quantifiable and predictable ways. The analytic approach presented here is used to estimate the distance at which runners will exhaust their glycogen stores as a function of running intensity. In so doing it also provides a basis for guidelines ensuring the safety and optimizing the performance of endurance runners, both by setting personally appropriate paces and by prescribing midrace fueling requirements for avoiding ‘the wall.’ The present analysis also sheds physiologically principled light on important standards in marathon running that until now have remained empirically defined: The qualifying times for the Boston Marathon

The effects of low and high glycemic index foods on exercise performance and beta-endorphin responses

Τhe aim of this study was to examine the effects of the consumption of foods of various glycemic index values on performance, β-endorphin levels and substrate (fat and carbohydrate) utilization during prolonged exercise. Eight untrained healthy males underwent, in a randomized counterbalanced design, three experimental conditions under which they received carbohydrates (1.5 gr. kg-1 of body weight) of low glycemic index (LGI), high glycemic index (HGI) or placebo. Food was administered 30 min prior to exercise. Subjects cycled for 60 min at an intensity corresponding to 65% of VO2max, which was increased to 90% of VO2max, then they cycled until exhaustion and the time to exhaustion was recorded. Blood was collected prior to food consumption, 15 min prior to exercise, 0, 20, 40, and 60 min into exercise as well as at exhaustion. Blood was analyzed for β-endorphin, glucose, insulin, and lactate. The mean time to exhaustion did not differ between the three conditions (LGI = 3.2 ± 0.9 min; HGI = 2.9 ± 0.9 min; placebo = 2.7 ± 0.7 min). There was a significant interaction in glucose and insulin response (P < 0.05) with HGI exhibiting higher values before exercise. β-endorphin increased significantly (P < 0.05) at the end of exercise without, however, a significant interaction between the three conditions. Rate of perceived exertion, heart rate, ventilation, lactate, respiratory quotient and substrate oxidation rate did not differ between the three conditions. The present study indicates that ingestion of foods of different glycemic index 30 min prior to one hour cycling exercise does not result in significant changes in exercise performance, β-endorphin levels as well as carbohydrate and fat oxidation during exercise

Effect of Mouth Rinsing and Ingestion of Carbohydrate Solutions on Mood and Perceptual Responses During Exercise

Background: The aim of this study was to investigate whether mouth rinsing or ingesting carbohydrate (CHO) solutions impact on perceptual responses during exercise. Methods: Nine moderately trained male cyclists underwent a 90-min glycogen-reducing exercise, and consumed a low CHO meal, prior to completing an overnight fast. A 1-h cycle time trial was performed the following morning. Four trials, each separated by 7days, were conducted in a randomized, counterbalanced study design: 15% CHO mouth rinse (CHOR), 7.5% CHO ingestion (CHOI), placebo mouth rinse (PLAR) and placebo ingestion (PLAI). Solution volumes (1.5ml·g-1 ingestion trials and 0.33ml·kg-1 rinsing trials) were provided after every 12.5% of completed exercise. Perceptual scales were used to assess affective valence (feeling scale, FS), arousal (felt arousal scale, FAS), exertion (ratings of perceived exertion, RPE) and mood (profile of mood states, POMS) before, during and immediately after exercise. Results: There was no difference in RPE (CHOI, 14.0±9; CHOR, 14.2±.7; PLAI, 14.6±1.8; PLAR, 14.6±2.0; P=0.35), FS (CHOI, 0.0±1.7; CHOR, -0.2±1.5; PLAI, -0.8±1.4; PLAR, -0.8±1.6; P0.15), or FAS (CHOI, 3.6±1.1; CHOR, 3.5±1.0; PLAI, 3.4±1.4; PLAR, 3.3±1.3; P=725) scores between trials. While overall POMS score did not appear to differ between trials, the 'vigour' subscale indicated that CHOI may facilitate the maintenance of 'vigour' scores over time, in comparison to the steady decline witnessed in other trials (P=0.04). There was no difference in time trial performance between trials (CHOI, 65.3±4.8min; CHOR, 68.4±3.9min; PLAI, 68.7±5.3min; PLAR, 68.3±5.2min; P=0.21) but power output was higher in CHOI (231.0±33.2 W) relative to other trials (221-223.6 W; Plt0.01). Conclusions: In a CHO-reduced state, mouth rinsing with a CHO solution did not impact on perceptual responses during high-intensity exercise in trained cyclists and triathletes. On the other hand CHO ingestion improved perceived ratings of vigour and increased power output during exercise

A randomized controlled trial to isolate the effects of fasting and energy restriction on weight loss and metabolic health in lean adults

Intermittent fasting may impart metabolic benefits independent of energy balance by initiating fasting-mediated mechanisms. This randomized controlled trial examined 24-hour fasting with 150% energy intake on alternate days for 3 weeks in lean, healthy individuals (0:150; n = 12). Control groups involved a matched degree of energy restriction applied continuously without fasting (75% energy intake daily; 75:75; n = 12) or a matched pattern of fasting without net energy restriction (200% energy intake on alternate days; 0:200; n = 12). Primary outcomes were body composition, components of energy balance, and postprandial metabolism. Daily energy restriction (75:75) reduced body mass (−1.91 ± 0.99 kilograms) almost entirely due to fat loss (−1.75 ± 0.79 kilograms). Restricting energy intake via fasting (0:150) also decreased body mass (−1.60 ± 1.06 kilograms; P = 0.46 versus 75:75) but with attenuated reductions in body fat (−0.74 ± 1.32 kilograms; P = 0.01 versus 75:75), whereas fasting without energy restriction (0:200) did not significantly reduce either body mass (−0.52 ± 1.09 kilograms; P ≤ 0.04 versus 75:75 and 0:150) or fat mass (−0.12 ± 0.68 kilograms; P ≤ 0.05 versus 75:75 and 0:150). Postprandial indices of cardiometabolic health and gut hormones, along with the expression of key genes in subcutaneous adipose tissue, were not statistically different between groups (P > 0.05). Alternate-day fasting less effectively reduces body fat mass than a matched degree of daily energy restriction and without evidence of fasting-specific effects on metabolic regulation or cardiovascular health

Effect of acute hypohydration on glycemic regulation in healthy adults : a randomized crossover trial

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