Does skeletal muscle carnitine availability influence fuel selection during exercise?

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.Fat and carbohydrate are the major fuel sources utilised for oxidative, mitochondrial ATP resynthesis during human skeletal muscle contraction. The relative contribution of these two substrates to ATP resynthesis and total energy expenditure during exercise can vary substantially, and is predominantly determined by fuel availability and exercise intensity and duration. For example, the increased ATP demand that occurs with an increase in exercise intensity is met by increases in both fat and carbohydrate oxidation up to an intensity of approximately 60–70 % of maximal oxygen consumption. When exercise intensity increases beyond this workload, skeletal muscle carbohydrate utilisation is accelerated, which results in a reduction and inhibition of the relative and absolute contribution of fat oxidation to total energy expenditure. However, the precise mechanisms regulating muscle fuel selection and underpinning the decline in fat oxidation remain unclear. This brief review will primarily address the theory that a carbohydrate flux-mediated reduction in the availability of muscle carnitine to the mitochondrial enzyme carnitine palmitoyltransferase 1, a rate-limiting step in mitochondrial fat translocation, is a key mechanism for the decline in fat oxidation during high-intensity exercise. This is discussed in relation to recent work in this area investigating fuel metabolism at various exercise intensities and taking advantage of the discovery that skeletal muscle carnitine content can be nutritionally increased in vivo in human subjects

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/

Increasing skeletal muscle carnitine availability does not alter the adaptations to high-intensity interval training

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Accepted manuscript online: 27 March 2017Increasing skeletal muscle carnitine availability alters muscle metabolism during steady-state exercise in healthy humans. We investigated whether elevating muscle carnitine, and thereby the acetyl-group buffering capacity, altered the metabolic and physiological adaptations to 24 weeks of high-intensity interval training (HIIT) at 100% maximal exercise capacity (Wattmax ). Twenty-one healthy male volunteers (age 23±2 years; BMI 24.2±1.1 kg/m(2) ) performed 2x3 minute bouts of cycling exercise at 100% Wattmax , separated by five minutes rest. Fourteen volunteers repeated this protocol following 24 weeks of HIIT and twice-daily consumption of 80g carbohydrate (CON) or 3g L-carnitine+carbohydrate (CARN). Before HIIT, muscle phosphocreatine (PCr) degradation (P<0.0001), glycogenolysis (P<0.0005), PDC activation (P<0.05), and acetylcarnitine (P<0.005) were 2.3, 2.1, 1.5 and 1.5-fold greater, respectively, in exercise bout two compared to bout one, whilst lactate accumulation tended (P<0.07) to be 1.5-fold greater. Following HIIT, muscle free carnitine was 30% greater in CARN vs CON at rest and remained 40% elevated prior to the start of bout two (P<0.05). Following bout two, free carnitine content, PCr degradation, glycogenolysis, lactate accumulation, and PDC activation were all similar between CON and CARN, albeit markedly lower than before HIIT. VO2max , Wattmax and work-output were similarly increased in CON and CARN, by 9, 15 and 23% (P<0.001). In summary, increased reliance on non-mitochondrial ATP resynthesis during a second bout of intense exercise is accompanied by increased carnitine acetylation. Augmenting muscle carnitine during 24 weeks of HIIT did not alter this, nor enhance muscle metabolic adaptations or performance gains beyond those with HIIT alone. This article is protected by copyright. All rights reserved.This research was supported by a BBSRC PhD studentship award for CS

Reply to LTE: Does caffeine truly raise muscle carnitine in humans?

This is the final version. Available from Wiley via the DOI in this record. University of Exete

Rebuttal from Marlou L. Dirks, Benjamin T. Wall and Francis B. Stephens

This is the final version. Available on open access from Wiley via the DOI in this recordThis article is part of a CrossTalk debate. Click the links to read the other articles in this debate: https://doi.org/10.1113/JP278219, https://doi.org/10.1113/JP279714, https://doi.org/10.1113/JP27822

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]

A single day of bed rest, irrespective of energy balance, does not affect skeletal muscle gene expression or insulin sensitivity

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The initial metabolic and molecular events that underpin disuse-induced skeletal muscle deconditioning, and the contribution of energy balance, remain to be investigated. Ten young, healthy males (age: 25 ± 1 y; BMI: 25.3 ± 0.8 kg m-2 ) underwent three 24 h laboratory-based experimental periods in a randomized, crossover manner: 1) controlled habitual physical activity with an energy-balanced diet (CON); 2) strict bed rest with a diet to maintain energy balance (BR-B); and 3) strict bed rest with a diet identical to CON, consequently resulting in positive energy balance. Continuous glucose monitoring was performed throughout each visit, with vastus lateralis muscle biopsies and an oral glucose tolerance test performed before and after. In parallel with muscle samples collected from a previous 7-day bed rest study, biopsies were used to examine expression of genes associated with the regulation of muscle mass and insulin sensitivity. A single day of bed rest, irrespective of energy balance, did not lead to overt changes in whole-body substrate oxidation, indices of insulin sensitivity (i.e. HOMA-IR (BR-B: from 2.7 ± 1.7 to 3.1 ± 1.5, P > 0.05), Matsuda (BR-B: from 5.9 ± 3.3 to 5.2 ± 2.9, P > 0.05)), or 24 h glycaemic control/variability compared to CON. Seven days of bed rest led to ∼30-55% lower expression of genes involved in insulin signalling, lipid storage/oxidation, and muscle protein breakdown, whereas no such changes were observed after one day of bed rest. In conclusion, more than one day of physical inactivity is required to observe the insulin resistance and robust skeletal muscle transcriptional responses associated with bed rest and consequent alterations in energy balance.BTW received internal funding from the College of Life and Environmental Sciences, University of Exeter, to support this project. None of the other authors received funding from any funding agency in the public, commercial or not-for-profit sectors to conduct this research

Monitoring Flower Visitation Networks and Interactions between Pairs of Bumble Bees in a Large Outdoor Flight Cage

This research was supported by a combined grant from the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the Engineering and Physical Sciences Research Council (BB/F52765X/1). While writing, ML was supported by the IDEX of the Federal University of Toulouse (Starting and Emergence grants), the Fyssen foundation and the CNRS. NER was supported as the Rebanks Family Chair in Pollinator Conservation by The W. Garfield Weston Foundation. LC was supported by ERC Advanced Grant SpaceRadarPollinator and by a Royal Society Wolfson Research Merit Award

The effect of various breath-hold techniques on the cardiorespiratory response to facial immersion in humans

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All data supporting the results of the paper are available as Supporting Information.NEW FINDINGS: What is the central question of this study? What is the effect of three repeated breath-hold techniques routinely used by freedivers, thought to manipulate arterial partial pressures of O2 and CO2 , on the cardiorespiratory and haematological response to breath-holding during facial immersion? What is the main finding and its importance? All three techniques increased breath-hold by a similar duration, probably owing to the similar marked increase in end-tidal O2 and decrease in end-tidal CO2 observed in all three trials before facial immersion. These were the only cardiorespiratory changes that were consistently manipulated before the maximal breath-hold. This would suggest that pronounced bradycardia and vasoconstriction of selective vascular beds are probably not obligatory for prolonging breath-hold duration. ABSTRACT: Repeated maximal breath-holds have been demonstrated to induce bradycardia, increase haematocrit and haemoglobin and prolong subsequent breath-hold duration by 20%. Freedivers use non-maximal breath-hold techniques (BHTs) to improve breath-hold duration. The aim of this study was to investigate the cardiorespiratory and haematological responses to various BHTs. Ten healthy men (34.5 ± 1.9 years) attended five randomized experimental trials and performed a 40 min period of quiet rest or one of three BHTs followed by a maximal breath-hold challenge during facial immersion in water at 30 or 10°C. Cardiovascular and respiratory parameters were measured continuously using finger plethysmography and breath-by-breath gas analysis, respectively, and venous blood samples were collected throughout. Facial immersion in cold water caused marked bradycardia (74.1 vs. 50.2 beats/min after 40 s) but did not increase breath-hold duration compared with warm water control conditions. Facial immersion breath-hold duration was 30.8-43.3% greater than the control duration when preceded by BHTs that involved repeated breath-holds of constant duration (P = 0.021), increasing duration (P  0.05). In conclusion, the duration of apnoea can be extended by manipulating blood gases through repeated prior breath-holds, but changes in cardiac output and red blood cell mass do not appear essential.Royal Nav

Association of postprandial postexercise muscle protein synthesis rates with dietary leucine: A systematic review.

This is the final version. Available from Wiley via the DOI in this record. DATA AVAILABILITY STATEMENT: The datasets generated and/or analyzed during the study implementation are available from the corresponding author upon request.BACKGROUND: Dietary protein ingestion augments post (resistance) exercise muscle protein synthesis (MPS) rates. It is thought that the dose of leucine ingested within the protein (leucine threshold hypothesis) and the subsequent plasma leucine variables (leucine trigger hypothesis; peak magnitude, rate of rise, and total availability) determine the magnitude of the postprandial postexercise MPS response. METHODS: A quantitative systematic review was performed extracting data from studies that recruited healthy adults, applied a bout of resistance exercise, ingested a bolus of protein within an hour of exercise, and measured plasma leucine concentrations and MPS rates (delta change from basal). RESULTS: Ingested leucine dose was associated with the magnitude of the MPS response in older, but not younger, adults over acute (0-2 h, r2  = 0.64, p = 0.02) and the entire postprandial (>2 h, r2  = 0.18, p = 0.01) period. However, no single plasma leucine variable possessed substantial predictive capacity over the magnitude of MPS rates in younger or older adults. CONCLUSION: Our data provide support that leucine dose provides predictive capacity over postprandial postexercise MPS responses in older adults. However, no threshold in older adults and no plasma leucine variable was correlated with the magnitude of the postexercise anabolic response.Beachbody LL