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Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization (2022)
Journal Article
Shur, N. F., Simpson, E. J., Crossland, H., Chivaka, P. K., Constantin, D., Cordon, S. M., …Greenhaff, P. L. (2022). Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization. Journal of Cachexia, Sarcopenia and Muscle, 13(6), 2999-3013. https://doi.org/10.1002/jcsm.13075

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... Read More about Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.

Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function (2020)
Journal Article
Atkins, R., Constantin-Teodosiu, D., Varadhan, K. K., Constantin, D., Lobo, D. N., & Greenhaff, P. L. (2021). Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function. Clinical Nutrition, 40(3), 1046-1051. https://doi.org/10.1016/j.clnu.2020.07.006

© 2020 The Author(s) Background & 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... Read More about Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function.

Mitochondrial DNA copy number associates with insulin sensitivity and aerobic capacity, and differs between sedentary, overweight middle-aged males with and without type 2 diabetes (2019)
Journal Article
Constantin-Teodosiu, D., Constantin, D., Pelsers, M. M., Verdijk, L. B., van Loon, L., & Greenhaff, P. (2019). Mitochondrial DNA copy number associates with insulin sensitivity and aerobic capacity, and differs between sedentary, overweight middle-aged males with and without type 2 diabetes. International Journal of Obesity, https://doi.org/10.1038/s41366-019-0473-2

Background/objectives: 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... Read More about Mitochondrial DNA copy number associates with insulin sensitivity and aerobic capacity, and differs between sedentary, overweight middle-aged males with and without type 2 diabetes.

Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men (2019)
Journal Article
Gharahdaghi, N., Rudrappa, S., Brook, M. S., Idris, I., Crossland, H., Hamrock, C., …Atherton, P. J. (2019). Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men. Journal of Cachexia, Sarcopenia and Muscle, 10(6), 1276-1294. https://doi.org/10.1002/jcsm.12472

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 (RE... Read More about Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men.

Do Antiretroviral Drugs Protect From Multiple Sclerosis By Inhibiting Expression Of MS-Associated Retrovirus? (2019)
Journal Article
Morandi, E., Tanasescu, R., Tarlington, R., Constantin-Teodosiu, D., & Gran, B. (2019). Do Antiretroviral Drugs Protect From Multiple Sclerosis By Inhibiting Expression Of MS-Associated Retrovirus?. Frontiers in Immunology, 9, https://doi.org/10.3389/fimmu.2018.03092

The expression of human endogenous retroviruses (HERVs) has been associated with Multiple Sclerosis (MS). The MS-related retrovirus (MSRV/HERV-W) has the potential to activate inflammatory immunity, which could promote both susceptibility and progres... Read More about Do Antiretroviral Drugs Protect From Multiple Sclerosis By Inhibiting Expression Of MS-Associated Retrovirus?.

Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans (2018)
Journal Article
Gaffney, C. J., Pollard, A., Barratt, T. F., Constantin-Teodosiu, D., Greenhaff, P. L., & Szewczyk, N. J. (2018). Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans. Aging, 10(11), 3382-3396. https://doi.org/10.18632/aging.101654

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,... Read More about Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans.

The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end points (2018)
Journal Article
Crossland, H., Skirrow, S., Puthucheary, Z. A., Constantin-Teodosiu, D., & Greenhaff, P. L. (2018). The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end points. Journal of Physiology, 597(5), 1259-1270. https://doi.org/10.1113/jp275444

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... Read More about The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: different routes to similar end points.

Increasing cardiac pyruvate dehydrogenase flux during chronic hypoxia improves acute hypoxic tolerance (2018)
Journal Article
Handzlik, M., Constantin-Teodosiu, D., Greenhaff, P. L., & Cole, M. (2018). Increasing cardiac pyruvate dehydrogenase flux during chronic hypoxia improves acute hypoxic tolerance. Journal of Physiology, 596(15), 3357-3369. https://doi.org/10.1113/JP275357

The pattern of metabolic reprogramming in chronic hypoxia shares similarities with that following myocardial infarction or hypertrophy, however the response of the chronically hypoxic heart to subsequent acute injury, and the role of metabolism is no... Read More about Increasing cardiac pyruvate dehydrogenase flux during chronic hypoxia improves acute hypoxic tolerance.

Maximal-intensity exercise does not fully restore muscle pyruvate dehydrogenase complex activation after 3 days of high-fat dietary intake (2018)
Journal Article
Constantin-Teodosiu, D., Cederblad, G., Bergstrom, M., & Greenhaff, P. L. (2019). Maximal-intensity exercise does not fully restore muscle pyruvate dehydrogenase complex activation after 3 days of high-fat dietary intake. Clinical Nutrition, 38(2), 948-953. https://doi.org/10.1016/j.clnu.2018.02.001

© 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism Background & aims: Exercise activates muscle pyruvate dehydrogenase complex (PDC), but moderate intensity exercise fails to fully activate muscle PDC after high-fat diet [... Read More about Maximal-intensity exercise does not fully restore muscle pyruvate dehydrogenase complex activation after 3 days of high-fat dietary intake.

Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery (2017)
Journal Article
Varadhan, K. K., Constantin-Teodosiu, D., Constantin, D., Greenhaff, P. L., & Lobo, D. N. (2017). Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery. Clinical Nutrition, 37(6, Part A), 2178-2185. https://doi.org/10.1016/j.clnu.2017.10.020

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 incr... Read More about Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery.

Muscle carnitine availability plays a central role in regulating fuel metabolism in the rodent (2017)
Journal Article
Porter, C., Constantin-Teodosiu, D., Constantin, D., Leighton, B., Poucher, S. M., & Greenhaff, P. L. (2017). Muscle carnitine availability plays a central role in regulating fuel metabolism in the rodent. Journal of Physiology, 595(17), 5765-5780. https://doi.org/10.1113/JP274415

The body carnitine pool is primarily confined to skeletal muscle, where it regulates carbohydrate (CHO) and fat usage. Mildronate (3-(2,2,2-trimethylhydrazinium)-propionate) inhibits carnitine synthesis and tissue uptake, but the impact of carnitine... Read More about Muscle carnitine availability plays a central role in regulating fuel metabolism in the rodent.

Peroxisome proliferator-activated receptor ? agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats (2017)
Journal Article
Crossland, H., Constantin-Teodosiu, D., Gardiner, S. M., & Greenhaff, P. (2017). Peroxisome proliferator-activated receptor ? agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats. Clinical Science, 131(13), 1437-1447. https://doi.org/10.1042/CS20170958

The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and c... Read More about Peroxisome proliferator-activated receptor ? agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats.

Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway (2017)
Journal Article
Ugun-Klusek, A., Tatham, M. H., Elkharaz, J., Constantin-Teodosiu, D., Lawler, K., Mohamed, H., …Bedford, L. (2017). Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway. Cell Death and Disease, 8(1), e2531-e2531. https://doi.org/10.1038/cddis.2016.443

The ubiquitin–proteasome system (UPS) and macroautophagy (autophagy) are central to normal proteostasis and interdependent in that autophagy is known to compensate for the UPS to alleviate ensuing proteotoxic stress that impairs cell function. UPS an... Read More about Continued 26S proteasome dysfunction in mouse brain cortical neurons impairs autophagy and the Keap1-Nrf2 oxidative defence pathway.

The effect of age and unilateral leg immobilisation for 2 weeks on substrate ulilisation during moderate-intensity exercise in human skeletal muscle (2016)
Journal Article
Vigelsø, A., Gram, M., Dybboe, R., Kuhlman, A., Prats, C., Greenhaff, P. L., …Helge, J. (2016). The effect of age and unilateral leg immobilisation for 2 weeks on substrate ulilisation during moderate-intensity exercise in human skeletal muscle. Journal of Physiology, 594(8), 2339-2358. https://doi.org/10.1113/JP271712

Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs dur... Read More about The effect of age and unilateral leg immobilisation for 2 weeks on substrate ulilisation during moderate-intensity exercise in human skeletal muscle.

Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression: Statin myalgia, muscle function and metabolism (2015)
Journal Article
Selby, A., Murton, A., Mallinson, J. E., Marimuthu, K., Murton, A. J., Selby, A. L., …Greenhaff, P. L. (2015). Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression: Statin myalgia, muscle function and metabolism. Journal of Physiology, 593(5), 1239-1257. https://doi.org/10.1113/jphysiol.2014.285577

Statins are associated with muscle myalgia and myopathy, which probably reduce habitual physical activity. This is particularly relevant to older people who are less active, sarcopaenic and at increased risk of statin myalgia. We hypothesised that st... Read More about Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression: Statin myalgia, muscle function and metabolism.

Preoperative carbohydrate supplementation attenuates post-surgery insulin resistance via reduced inflammatory inhibition of the insulin-mediated restraint on muscle pyruvate dehydrogenase kinase 4 expression (2014)
Journal Article
Fosse Gjessing, P., Constantin-Teodosiu, D., Hagve, M., Lobo, D. N., Revhaug, A., & Irtun, Ø. (2015). Preoperative carbohydrate supplementation attenuates post-surgery insulin resistance via reduced inflammatory inhibition of the insulin-mediated restraint on muscle pyruvate dehydrogenase kinase 4 expression. Clinical Nutrition, 34(6), 1177-1183. https://doi.org/10.1016/j.clnu.2014.12.004

The integrin-adhesome is required to maintain muscle structure, mitochondrial ATP production, and movement forces in Caenorhabditis elegans (2014)
Journal Article
Etheridge, T., Rahman, M., Gaffney, C. J., Shaw, D., Shephard, F., Magudia, J., …Szewcyzk, N. (2015). The integrin-adhesome is required to maintain muscle structure, mitochondrial ATP production, and movement forces in Caenorhabditis elegans. FASEB Journal, 29(4), 1235-1246. https://doi.org/10.1096/fj.14-259119

The integrin-adhesome network, which contains >150 proteins, is mechano-transducing and located at discreet positions along the cell-cell and cell-extracellular matrix interface. A small subset of the integrin-adhesome is known to maintain normal mus... Read More about The integrin-adhesome is required to maintain muscle structure, mitochondrial ATP production, and movement forces in Caenorhabditis elegans.

The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity (2012)
Journal Article
Foxler, D. E., Bridge, K. S., James, V., Webb, T. M., Mee, M., Wong, S. C. K., …Sharp, T. V. (2012). The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity. Nature Cell Biology, 14(2), 201-208. https://doi.org/10.1038/ncb2424

There are three prolyl hydroxylases (PHD1, 2 and 3) that regulate the hypoxia-inducible factors (HIFs), the master transcriptional regulators that respond to changes in intracellular O2 tension1,2. In high O2 tension (normoxia) the PHDs hydroxylate t... Read More about The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity.