Francis B Stephens's research while affiliated with University of Exeter and other places
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Publications (93)
Background:
It remains unclear whether non-animal-derived dietary protein sources (and therefore vegan diets) can support resistance training-induced skeletal muscle remodeling to the same extent as animal-derived protein sources.
Methods:
In Phase 1, 16 healthy young adults (m = 8, f = 8; age: 23 ± 1 y; BMI: 23 ± 1 kg/m2) completed a 3-d dietar...
Increasing skeletal muscle carnitine content can manipulate fuel metabolism and improve exercise performance. Intravenous insulin infusion during hypercarnitinemia increases plasma carnitine clearance and Na+‐dependent muscle carnitine accretion, likely via stimulating Na+/K+ ATPase pump activity. We hypothesized that the ingestion of high‐dose caf...
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 importa...
Ingestion of mycoprotein stimulates skeletal muscle protein synthesis (MPS) rates to a greater extent than concentrated milk protein when matched for leucine content, potentially attributable to the whole-food nature of mycoprotein. We hypothesised that bolus ingestion of mycoprotein as part of its whole food matrix would stimulate MPS rates to a g...
New findings:
What is the central question of this study? Does acute ketone monoester supplementation enhance the recovery of muscle force and modulate circulating cytokine concentrations after muscle-damaging eccentric exercise? What is the main finding and its importance? We report that ketone monoester supplementation increased plasma β-hydroxy...
Background
Bed rest (BR) reduces whole‐body insulin‐stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance.
Methods
Healthy males (n = 10, 24.0 ± 1.3 years), maintained in e...
To mitigate the age-related decline in skeletal muscle quantity and quality, and the associated negative health outcomes, it has been proposed that dietary protein recommendations for older adults should be increased alongside an active lifestyle and/or structured exercise training. Concomitantly, there are growing environmental concerns associated...
Introduction
Bed-rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism. However, little is known about metabolic adaptation from acute to chronic BR, particularly when volunteers are maintained in energy balance.
Methods
Healthy males (n=10, 24±1.25 years) maintained in energy balance underwent 3 d...
Background
Obesity and insulin resistance are associated with an impaired sensitivity to anabolic stimuli such as dietary protein (anabolic resistance). Omega-3 polyunsaturated fatty acids (n-3 PUFA) may be protective against the deleterious effects of saturated fatty acids (SFA) on insulin resistance. However, the contribution of excess fat consum...
Background & Aims
Elevated circulating uric acid concentrations have been linked to various cardio-metabolic diseases. Bolus consumption of a nucleotide-rich dietary protein source increases postprandial serum uric acid concentrations. We assessed the impact of twice-daily nucleotide-rich mixed-meal consumption for one week on postabsorptive serum...
![Plasma 2 H and myofibrillar protein-bound [ 2 H]-alanine enrichments...](profile/Tom-Jameson/publication/357896784/figure/tbl1/AS:1131706866253826@1646831351399/Plasma-2-H-and-myofibrillar-protein-bound-2-H-alanine-enrichments-over-the-acute_Q320.jpg)
Factors underpinning the time-course of resistance-type exercise training (RET) adaptations are not fully understood. The present study hypothesized that consuming a twice-daily protein-polyphenol beverage (PPB; n=15; age, 24 ± 1 years; BMI, 22.3 ± 0.7 kg·m ⁻² ) previously shown to accelerate recovery from muscle damage and increase daily myofibril...
Introduction:
Short-term disuse leads to muscle loss driven by lowered daily myofibrillar protein synthesis (MyoPS). However, disuse commonly results from muscle damage, and its influence on muscle deconditioning during disuse is unknown.
Methods:
21 males (20±1 y, BMI=24±1 kg·m-2 (±SEM)) underwent 7 days of unilateral leg immobilization immedia...
The rs2802292, rs2764264 and rs13217795 variants of FOXO3 have been associated with extreme longevity in multiple human populations, but the mechanisms underpinning this remain unclear. We aimed to characterise potential effects of longevity-associated variation on the expression and mRNA processing of the FOXO3 gene. We performed a comprehensive a...
Context
The early events regulating the remodelling programme following skeletal muscle damage are poorly understood.
Objective
The objective of this study was to determine the association between myofibrillar protein synthesis (myoPS) and nuclear factor-kappa B (NF-κB) signalling by nutritionally accelerating recovery of muscle function following...
Key points:
The trajectory, magnitude and localisation of metabolic perturbations caused by immobilisation (IMM) are unresolved. Forearm glucose uptake (FGU) in response to glucose feeding was determined in healthy men before and during 72 hrs of forearm IMM, and the same measurements were made in the non-IMM contralateral limb at baseline and 72...
Intramyocellular lipid (IMCL) utilization is impaired in older individuals, and IMCL accumulation is associated with insulin resistance. We hypothesized that increasing muscle total carnitine content in older men would increase fat oxidation and IMCL utilization during exercise, and improve insulin sensitivity. Fourteen healthy older men (69 ± 1 ye...
Background and aims
We have previously shown reduced protein balance in response to nutrition in paediatric Crohn's disease (CD) in remission, associated with reduced lean mass (sarcopenia) and reduced protein intake in males. We aim to compare skeletal muscle metabolic response to feeding in adult active CD and healthy volunteers.
Methods
Eight C...
The contribution of myofibrillar protein synthesis (MyoPS) to recovery from skeletal muscle damage in humans is unknown. Recreationally active males and females consumed a daily protein-polyphenol beverage targeted at increasing amino acid availability and reducing inflammation (PPB; n=9), both known to affect MyoPS, or an isocaloric placebo (PLA;...
Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (age 66±1 y; BMI 24±1 kg·m ⁻² ; m=12, f=7) parti...
Background:
We have shown that ingesting a large bolus (70 g) of the fungal-derived, whole food mycoprotein robustly stimulates muscle protein synthesis (MPS) rates.
Objective:
The aim of this study was to determine if a lower dose (35 g) of mycoprotein enriched with branched-chain amino acids (BCAAs) stimulates MPS to the same extent as 70 g of...
Mycoprotein consumption has been shown to improve acute postprandial glycaemic control and decrease circulating cholesterol concentrations. We investigated the impact of incorporating mycoprotein into the diet on insulin sensitivity (IS), glycaemic control and plasma lipoprotein composition. Twenty healthy adults participated in a randomised, paral...
Background:
Mycoprotein is a fungal-derived sustainable protein-rich food source, and its ingestion results in systemic amino acid and leucine concentrations similar to that following milk protein ingestion.
Objective:
We assessed the mixed skeletal muscle protein synthetic response to the ingestion of a single bolus of mycoprotein compared with...
Circulating uric acid concentrations have been linked to various metabolic diseases. Consumption of large boluses of nucleotides increases serum uric acid concentrations. We investigated the effect of a nucleotide-rich mixed meal on postprandial circulating uric acid, glucose, and insulin responses. Ten healthy adults participated in a randomised,...
Background:
Pre-exercise supplements containing low doses of caffeine improve endurance exercise performance, but the most efficacious time for consumption before intense endurance exercise remains unclear, as does the contribution of caffeine metabolism.
Methods:
This study assessed the timing of a commercially available supplement containing 2...
Background:
Intensive care unit (ICU)-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 h o...
The world's population is expanding, leading to an increased global requirement for dietary protein to support health and adaptation in various populations. Though a strong evidence base supports the nutritional value of animal-derived dietary proteins, mounting challenges associated with sustainability of these proteins have led to calls for the i...
Intensive care unit-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional-electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 of ICU admission may i...
Context
Physical inactivity and high-fat overfeeding have been shown to independently induce insulin resistance.
Objective
Establish the contribution of muscle disuse and lipid availability to the development of inactivity-induced insulin resistance. Design, setting, participants, and interventions: Twenty healthy males underwent seven days of for...
Intensive care unit-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional-electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 of ICU admission may i...
Background & aims:
An inability to respond to nutrition could be implicated in low muscle mass in Crohn's disease. We aim to determine skeletal muscle metabolic response to feeding in Crohn's disease and healthy volunteers.
Methods:
Twenty asymptomatic Crohn's disease participants (15.6 ± 0.5 yrs; BMI 20.6 ± 0.9 kg/m2); 9 with active disease (fa...
Mycoprotein is an alternative, nutritious protein source with a meat-like texture made from Fusarium venenatum, a naturally occurring fungus. Its unique method of production yields a significantly reduced carbon and water footprint relative to beef and chicken. Mycoprotein, sold as Quorn, is consumed in 17 countries, including the United States. In...
Substituting meat/fish for mycoprotein for one week does not affect indices of metabolic health irrespective of dietary nucleotide load or serum uric acid concentrations in healthy young adults - Volume 77 Issue OCE4 - M. Coelho, A.J. Monteyne, M.L. Dirks, T.J.A. Finnigan, F.B. Stephens, B.T. Wall
Introduction
Sarcopenia is common in active Crohn’s disease (CD) and still prevalent in remission. This can lead to fatigue, physical inactivity and poor quality of life but the aetiology is unclear. We aimed to investigate the association between sarcopenia and anabolic resistance (AR) and insulin resistance (IR), and the role of physical activity...
New findings:
What is the central question of this study? The role of FGF21 as an exercise-induced myokine remains controversial. The aim of this study was to determine whether eccentric exercise would augment the release of FGF21 and/or its regulatory enzyme Fibroblast Activation Protein (FAP) from skeletal muscle tissue into the systemic circula...
New findings:
What is the central question of this study? What are the initial metabolic and molecular events that underpin bed rest-induced skeletal muscle deconditioning, and what is the contribution of energy balance? What is the main finding and its importance? A single day of bed rest, irrespective of energy balance, did not lead to overt cha...
Background
Sarcopenia is common in active Crohn’s disease (CD) and still prevalent in remission. This can lead to fatigue, physical inactivity and poor quality of life. The aetiology is unclear. Low levels of physical activity, inability to respond to anabolic stimuli such as food (anabolic resistance, AR) and insulin resistance (IR) could all be i...
The molecular and metabolic mechanisms underlying the increase in insulin sensitivity (i.e. increased insulin-stimulated skeletal muscle glucose uptake, phosphorylation and storage as glycogen) observed from 12 to 48 h following a single bout of exercise in humans remain unresolved. Moreover, whether these mechanisms differ with age is unclear. It...
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 in...
Context
Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose and sucrose all reported to increase plasma levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin.
Objective
The aim of this study was to examine the co...
This study investigated how acute restoration of normoglycaemia affected energy metabolism during exercise in nonobese patients with type 2 diabetes. Six subjects (mean ± SEM) aged 56.2 ± 2.7 years, with a BMI of 24.5 ± 1.5 kg/m ² and a VO 2 peak of 28.7 ml/kg/min, attended the lab on two randomised occasions for a four-hour resting infusion of ins...
The aim of this study was to examine the temporal relationship between intramyocellular lipid (IMCL) content and the expression of genes associated with IMCL turnover, fat metabolism, and inflammation during recovery from an acute bout of resistance type exercise in old versus young men. Seven healthy young (23±2years, 77.2±2.9kg) and seven healthy...
Increasing 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 exe...
Introduction:
The loss of muscle is common in patients with advanced non-small-cell lung cancer (NSCLC) and contributes to the high morbidity and mortality of this group. The exact mechanisms behind the muscle loss are unclear.
Patients and methods:
To investigate this, 4 patients with stage IV NSCLC who met the clinical definitions for sarcopen...
Insulin resistance is closely related to intramyocellular lipid (IMCL) accumulation, and both are associated with increasing age. It remains to be determined to what extent perturbations in IMCL metabolism are related to the ageing process per se. On two separate occasions whole-body and muscle insulin sensitivity (euglycaemic hyperinsulinaemic cla...
Background:
Increasing skeletal muscle carnitine content represents an appealing intervention in conditions of perturbed lipid metabolism such as obesity and type 2 diabetes but requires chronic l-carnitine feeding on a daily basis in a high-carbohydrate beverage.
Objective:
We investigated whether whey protein ingestion could reduce the carbohy...
Rahimi et al. (1) state that “whether fatty acids induce [muscle] insulin resistance by decreasing PDH [pyruvate dehydrogenase complex] flux remains unknown” and “the role of PDH and mitochondrial oxidative substrate selection in the regulation of basal and insulin-stimulated muscle glucose metabolism has not been directly assessed in vivo.” Theref...
The ability to maintain skeletal muscle mass appears to be impaired in insulin resistant conditions that are characterised by muscle lipid accumulation, such as type 2 diabetes. The present study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7 h intraven...
Acylcarnitine accumulation in skeletal muscle and plasma has been observed in numerous models of mitochondrial lipid overload and insulin resistance. Fish oil omega-3 polyunsaturated fatty acids (n3PUFA) are thought to protect against lipid-induced insulin resistance. The present study tested the hypothesis that addition of n3PUFA to an intravenous...
We sought to ascertain the time-course of transcriptional events that occur in human skeletal muscle at the outset of resistance exercise (RE) training in RE naïve individuals, and determine if the magnitude of response was associated with exercise induced muscle damage. Sixteen RE naïve males were recruited, 8 underwent 2 sessions of 5x30 maximum,...
This chapter focuses on the role of creatine and phosphorylcreatine (PCr) in skeletal muscle energetics. It identifies the conditions where PCr availability can influence muscle contractile function. This sets the scene for situations where there may be a benefit from creatine supplementation. The chapter considers the efficacy of creatine suppleme...
Fat and carbohydrate are the primary fuel sources for mitochondrial ATP production in human skeletal muscle during endurance exercise. However, fat exhibits a relatively low maximal rate of oxidation in vivo, which begins to decline at around 65% of maximal oxygen consumption (VO2max) when muscle glycogen becomes the major fuel. It is thought that...
Twelve weeks of daily L-carnitine and carbohydrate feeding in humans increases skeletal muscle total carnitine content, and prevents body mass accrual associated with carbohydrate feeding alone. Here we determined the influence of L-carnitine and carbohydrate feeding on
energy metabolism, body fat mass andmuscle expression of fuel metabolism genes....
Physiological hyperglycaemia and hyperinsulinaemia are strong modulators of gene expression, which underpins some of their well known effects on insulin action and energy metabolism. The aim of this study was to examine whether acute in vivo exposure of healthy humans to hyperinsulinaemia and hyperglycaemia have independent or additive effects on e...
Fasting increases lipid flux into mitochondria causing excessive β-oxidation, carnitine acylation and impaired cellular glucose uptake. Preoperative carbohydrate treatment (PCT) attenuates postoperative insulin resistance, but mechanisms underlying this and the effects on carnitine metabolism remain largely unknown.
Pre-, intra- and-postoperative (...
High-fat feeding inhibits pyruvate dehydrogenase complex (PDC)-controlled carbohydrate (CHO) oxidation, which contributes to muscle insulin resistance. We aimed to reveal molecular changes underpinning this process in resting and exercising humans. We also tested whether pharmacological activation of PDC overrides these diet-induced changes. Health...
The effect of a whey protein- and carbohydrate (CHO)-enriched diet on the rate of muscle glycogen resynthesis after a soccer match was examined. Sixteen elite soccer players were randomly assigned to a group ingesting a diet rich in carbohydrates and whey protein [CHO, protein, and fat content was 71, 21, and 8E%, respectively; high content of carb...
Reduced skeletal muscle free coenzyme A (CoASH) availability may decrease the contribution of fat oxidation to ATP production during high-intensity, submaximal exercise or, alternatively, limit pyruvate dehydrogenase complex (PDC) flux and thereby carbohydrate oxidation. Here we attempted to increase the muscle CoASH pool in humans, via pantothenic...
Ninety-five percent of the body carnitine pool resides in skeletal muscle where it plays a vital role in fuel metabolism. However, vegetarians obtain negligible amounts of carnitine from their diet.
We tested the hypothesis that muscle carnitine uptake is elevated in vegetarians compared with that in nonvegetarians to maintain a normal tissue carni...
The aim of this study was to examine maximal voluntary knee-extensor contraction force (MVC force), sarcoplasmic reticulum (SR) function and muscle glycogen levels in the days after a high-level soccer game when players ingested an optimised diet. Seven high-level male soccer players had a vastus lateralis muscle biopsy and a blood sample collected...
We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 wee...
