Paul L Greenhaff

Paul L Greenhaff
University of Nottingham | Notts · School of Life Sciences

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356
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Publications

Publications (356)
Article
Full-text available
Ageing limits growth capacity of skeletal muscle (e.g. in response to resistance exercise), but the role of satellite cell (SC) function in driving this phenomenon is poorly defined. Younger (Y) (~ 23 years) and older (O) men (~ 69 years) (normal-weight BMI) underwent 6 weeks of unilateral resistance exercise training (RET). Muscle biopsies were ta...
Article
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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. Healthy males (n = 10, 24.0 ± 1.3 years), maintained in energy balance, under...
Article
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Exercise training can induce adaptive changes to tendon tissue both structurally and mechanically; however, the underlying compositional changes that contribute to these alterations remain uncertain in humans, particularly in the context of the ageing tendon. The aims of the present study were to determine the molecular changes with ageing in patel...
Conference Paper
Full-text available
Introduction: Elective surgery induces skeletal muscle wasting driven by an imbalance between muscle protein synthesis and muscle protein breakdown. From examination of diverse stable isotope tracer techniques, the dynamic processes driving this imbalance are unclear. This meta-analysis aimed to investigate the mechanistic driver(s) of postoperativ...
Article
Introduction Immobility can lead to rapid reductions in muscle size, strength and function. Understanding these changes could inform interventions to prevent or slow decline. This longitudinal study aimed to assess the extent of muscle changes in older patients admitted with fragility fractures where clinical management was immobilisation (non-weig...
Article
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Background and aims Elective surgery induces skeletal muscle wasting driven by an imbalance between muscle protein synthesis and breakdown. From examination of diverse stable isotope tracer techniques, the dynamic processes driving this imbalance are unclear. This meta-analysis aimed to elucidate the mechanistic driver(s) of postoperative protein c...
Article
Background Fatigue perception and exercise intolerance are common in inflammatory bowel disease (IBD). The mechanisms are unknown, although physical deconditioning is greater in fatigued relative to non-fatigued patients, suggesting an aetiological role for deconditioning. To assess peripheral muscle quality in Crohn’s disease (CD), we quantified t...
Preprint
Elevated plasma leucine, isoleucine and valine (BCAA) are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention.Fa...
Article
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Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy, and insulin resistance with age and disease in humans, little is known about the mechanisms respon...
Article
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The molecular mechanisms by which free fatty acids (FFA) inhibit muscle glucose oxidation is still elusive. We recently showed that C2C12 myotubes treated with palmitate (PAL) presented with greater protein expression levels of PDK4 and transcription factors PPARα and PPARδ and lower p-FOXO/t-FOXO protein ratios when compared to control. This was c...
Article
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COPD patients exhibit lower peak oxygen consumption (V̇O 2 PEAK ), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic ex...
Article
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The peroxisome proliferator-activated receptor (PPAR) family of transcription factors has been demonstrated to play critical roles in regulating fuel selection, energy expenditure and inflammation in skeletal muscle and other tissues. Activation of PPARs, through endogenous fatty acids and fatty acid metabolites or synthetic compounds, has been dem...
Article
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Background: Fatigue is the inability to achieve or maintain an expected work output resulting from central or peripheral mechanisms. The prevalence of inflammatory bowel disease (IBD) fatigue can reach 86% in active disease, persisting in 50%-52% of patients with mild to inactive disease. Fatigue is the commonest reason for work absence in IBD, an...
Article
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Resistance exercise training (RET) is well-known to counteract negative age-related changes in both muscle and tendon tissue. Traditional RET consists of both concentric (CON) and eccentric (ECC) contractions; nevertheless, isolated ECC contractions are metabolically less demanding and, thus, may be more suitable for older populations. However, whe...
Conference Paper
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Deuterium spectra of the human calf were obtained at natural abundance, at 3 T field strength. Two peaks with a chemical shift separation of 3.5 ppm were observed, corresponding to water and lipids, and their relaxation times T1 and T2* were measured using a transceive surface coil. Utilising the complex data to fit spectral lines, including indepe...
Article
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Carbohydrate metabolism in heart failure shares similarities to that following hypoxic exposure, and is thought to maintain energy homeostasis in the face of reduced O2 availability. As part of these in vivo adaptations during sustained hypoxia, the heart upregulates and maintains a high glycolytic flux, but the underlying mechanism it is still elu...
Article
In the United Kingdom (UK), it is projected that by 2035 people aged >65 years will make up 23% of the population, with those aged >85 years accounting for 5% of the total population. Ageing is associated with progressive changes in muscle metabolism and a decline in functional capacity, leading to a loss of independence. Muscle metabolic changes a...
Article
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...
Article
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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...
Article
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High‐load eccentric training reputedly produces greater muscle hypertrophy than concentric training, possibly due to greater loading and/or inflammation. We quantified the temporal impact of combined maximal concentric‐eccentric training vs maximal concentric training on muscle cross‐sectional area (CSA), volume and targeted mRNA expression (93 tra...
Article
Introduction Skeletal muscle is a major site for whole-body glucose disposal, and determination of skeletal muscle glucose uptake is an important metabolic measurement, particularly in research focussed on interventions that impact muscle insulin sensitivity. Calculating arterial-venous difference in blood glucose can be used as an indirect measure...
Article
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Leucine, isoleucine and valine (i.e., the branched chain amino acids, BCAA) play a key role in the support and regulation of tissue protein regulation and also as energy substrates. However, positive relationships exist between elevated levels of BCAA and insulin resistance (IR). Thus, we sought to investigate the links between fasting plasma BCAA...
Article
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Background sarcopenia is the loss of muscle mass and quality and is diagnosed using measures of muscle strength, size and mass. We evaluated the literature on whether sarcopenia measures are predictive of motor outcomes in older people in clinical settings. Methods electronic databases (MEDLINE Ovid, EMBASE, CINAHL and Web of Science) were searche...
Article
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Introduction: Knee pain due to osteoarthritis (OA) is a common cause of disability. The UK National Institute for Health and Care Excellence OA guidelines recommend education, exercise and weight loss advice (if overweight) as core interventions before pharmacological adjuncts. However, implementation of these in primary care is often suboptimal....
Article
Background Eccentric cycling (ECC) may be an attractive exercise modality in COPD due to both low cardiorespiratory demand and perception of effort compared to conventional concentric cycling (CON) at matched mechanical loads. However, it is unknown whether ECC can be performed by individuals with COPD at an intensity able to cause sufficient metab...
Article
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The mechanisms behind the reduction in muscle pyruvate dehydrogenase complex (PDC)-controlled carbohydrate (CHO) oxidation during chronic high-fat dietary intake are poorly understood, as is the basis of CHO oxidation restoration during muscle contraction. C2C12 myotubes were treated with (300 µM) palmitate or without (control) for 16 h in the pres...
Conference Paper
The greater decline in force steadiness (FS) observed in older males (Tracy and Enoka 2002), is indicative of a sex-specific attenuation of motor control (Castronovo et al. 2018). There is growing evidence that FS (Jakobi et al. 2018) and recruitment strategies (Nishikawa et al. 2017) in young adults are also sexually dimorphic. Increases in force...
Preprint
Rheumatoid arthritis (RA) is accompanied by pain, inflammation and muscle weakness. Skeletal muscle inflammation and inactivity are independently associated with muscle insulin resistance and atrophy. Our objective was to identify early molecular and biochemical markers in muscle from a rodent model of RA relative to control and subsequently identi...
Article
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Rheumatoid arthritis (RA) is accompanied by pain, inflammation and muscle weakness. Skeletal muscle inflammation and inactivity are independently associated with muscle insulin resistance and atrophy. Our objective was to identify early molecular and biochemical markers in muscle from a rodent model of RA relative to control and subsequently identi...
Article
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Background and aims This post hoc study aimed to determine whether major elective abdominal surgery had any acute impact on mitochondrial pyruvate dehydrogenase complex (PDC) activity and maximal mitochondrial ATP production rates (MAPR) in a large muscle group (vastus lateralis -VL) distant to the site of surgical trauma. Methods Fifteen patients...
Article
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Ageing compromises skeletal muscle mass and function through poorly defined molecular aetiology. Here we have used untargeted metabolomics using UHPLC-MS to profile muscle tissue from young (n=10, 25±4y), middle aged (n=18, 50±4y) and older (n=18, 70±3y) men and women (50:50). Random Forest was used to prioritise metabolite features most informativ...
Article
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The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, car...
Article
Objective: Myokines, such as Irisin, have been purported to exert physiological effects on skeletal muscle in an autocrine/paracrine fashion. In this study, we aimed to investigate the mechanistic role of in vivo Fndc5/Irisin upregulation in muscle. Methods: Overexpression (OE) of Fndc5 in rat hind-limb muscle was achieved by in vivo electro-tra...
Article
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Increased risk of type 2 diabetes mellitus (T2DM) is linked to impaired muscle mitochondrial function and reduced mitochondrial DNA copy number (mtDNAnum). However, studies have failed to control for habitual physical activity levels, which directly influences both mtDNA copy number and insulin sensitivity. We, therefore, examined whether physical...
Article
Background and aims Malnutrition has been recognized as a major risk factor for adverse postoperative outcomes. The ESPEN Symposium on perioperative nutrition was held in Nottingham, UK, on 14-15 October 2018 and the aims of this document were to highlight the scientific basis for the nutritional and metabolic management of surgical patients. Meth...
Article
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Background: In an ageing population, pain, frailty and disability frequently coexist across a wide range of musculoskeletal diagnoses, but their associations remain incompletely understood. The Investigating Musculoskeletal Health and Wellbeing (IMH&W) study aims to measure and characterise the development and progression of pain, frailty and disa...
Chapter
Animal models of overt statin myopathy reveal clear negative effects on muscle protein and carbohydrate metabolism, which appear to be linked to changes in Akt/FOXO signalling. Forcibly increasing muscle carbohydrate flux under these conditions by pharmacological means blocks statin myopathy. Human volunteer research has delivered less definitive m...
Conference Paper
Background Eccentric cycling (ECC) may be an attractive exercise modality in COPD due to lower cardiorespiratory demand and perception of effort compared to conventional concentric cycling (CON) at equivalent mechanical workloads. However, it is unknown whether ECC can be performed by individuals with COPD at an intensity able to induce metabolic a...
Article
Full-text available
Introduction Knee osteoarthritis (OA) is the most common joint disease worldwide. As of today, there are no disease-modifying drugs, but there is evidence that muscle strengthening exercises can substantially reduce pain and improve function in this disorder, and one very well tested physiotherapy protocol is the ‘Better Management of Patients with...
Poster
Background: Eccentric cycling (ECC) may be an attractive exercise modality in COPD due to both low cardiorespiratory demand and perception of effort compared to conventional concentric cycling (CON). However, it is unknown whether ECC can be performed by individuals with COPD at an intensity able to induce metabolic adaptation. Methods: 13 individ...
Article
Full-text available
Background: The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RET). Nonetheless, the efficacy and physiological and molecular impacts of T therapy adjuvant to sho...
Conference Paper
Generation of muscle force relies on a combination of altered motor unit firing rates, and recruitment through a progressively increasing range of sizes. Alterations in these mechanisms may influence muscle functional decline in the fatigued and damaged state. Although eccentric exercise elicits a more significant loss of function, muscle damage an...
Article
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Background: Voluntary resistance exercise (RE) training increases muscle mass and strength in patients with chronic obstructive pulmonary disease (COPD). Nonvolitional transcutaneous neuromuscular electrical stimulation (NMES) may be an alternative strategy for reducing ambulatory muscle weakness in patients unable to perform RE training, but littl...
Article
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Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden. C. elegans, a model organism for investigating the mechanisms of ageing, also displays sarcopenia, but the underlying mechanism(s) remain elusive. Here, we use C. elegans natural scaling of lifespan in response to temperature to examine the relationshi...
Article
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Objectives To characterise the sketetal muscle metabolic phenotype during early critical illness. Methods Vastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5). Measurements and main results From...
Article
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Loss of muscle mass and insulin sensitivity are common phenotypic traits of immobilisation and increased inflammatory burden. The suppression of muscle protein synthesis is the primary driver of muscle mass loss in human immobilisation, and includes blunting of post‐prandial increases in muscle protein synthesis. However, the mechanistic drivers of...
Conference Paper
Rationale – Eccentric exercise, comprising muscle contractions during active lengthening, demonstrates a lower cardiopulmonary demand than traditional concentric exercise. It is therefore an attractive training modality for a disease population, particularly chronic respiratory disease where maximal exercise is often limited by ventilatory constrai...
Article
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Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transien...
Article
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Background & aims: Exercise activates muscle pyruvate dehydrogenase complex (PDC), but moderate intensity exercise fails to fully activate muscle PDC after high-fat diet [1]. We investigated whether maximal intensity exercise overcomes this inhibition. Methods: Quadriceps femoris muscle biopsy samples were obtained from healthy males at rest, an...
Article
Full-text available
Key points: The cardiac metabolic reprogramming seen in heart diseases such as myocardial infarction and hypertrophy shares similarities with that seen in chronic hypoxia, but understanding of how the hypoxic heart responds to further hypoxic challenge - hypoxic tolerance - is limited. The pyruvate dehydrogenase complex serves to control irreversi...
Article
Full-text available
Background & aims: Postoperative hyperglycaemia is common in patients having major surgery and is associated with adverse outcomes. This study aimed to determine whether bacteraemia contributed to postoperative systemic inflammation, and whether increases in the expression of muscle mRNAs and proteins reflecting increased muscle inflammation, atro...
Article
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We thank Dr Dankel and colleagues for their letter (Dankel et al. 2017) concerning our manuscript Franchi et al. 2017 (1) . In summary, while acknowledging the new insight the work provides regarding the association between ultrasound-based imaging and MRI when quantifying increases in muscle mass with resistance exercise training, Dankel and colle...
Article
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Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest leucine boluses shortly after meals may prolong MPS and delay onset of a "muscle-full" state. However, the effects of nutrient "top-ups" in humans, and particularly older adults where deficits exist, have not been...
Article
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Background: The impact of resistance exercise training (RE-T) across the life span is poorly defined. Methods: To resolve this, we recruited three distinct age cohorts of young (18-28 years; n = 11), middle-aged (45-55 years; n = 20), and older (nonsarcopenic; 65-75 years; n = 17) individuals to a cross-sectional intervention study. All subjects...