Derek Ball | Heriot-Watt University (original) (raw)

Papers by Derek Ball

Research paper thumbnail of PHOSPHO1 is a skeletal regulator of insulin resistance and obesity

BMC Biology, 2020

Background The classical functions of the skeleton encompass locomotion, protection and mineral h... more Background The classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regulator of metabolism. The bone-specific phosphatase, Phosphatase, Orphan 1 (PHOSPHO1), which is indispensable for bone mineralisation, has been recently implicated in the regulation of energy metabolism in humans, but its role in systemic metabolism remains unclear. Here, we probe the mechanism underlying metabolic regulation by analysing Phospho1 mutant mice. Results Phospho1−/− mice exhibited improved basal glucose homeostasis and resisted high-fat-diet-induced weight gain and diabetes. The metabolic protection in Phospho1−/− mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated from Phospho1−/− mice were enriched for genes associated with energy metabolism and diabetes; Phospho1 both directly and indirectly inte...

Research paper thumbnail of PHOSPHO1, a novel skeletal regulator of insulin resistance and obesity

The skeleton is recognised as a key endocrine regulator of metabolism. Here we show that mice lac... more The skeleton is recognised as a key endocrine regulator of metabolism. Here we show that mice lacking the bone mineralization enzyme PHOSPHO1 (Phospho1-/-) exhibited improved basal glucose homeostasis and resisted high-fat-diet induced weight gain and diabetes. The metabolic protection inPhospho1-/-mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated fromPhospho1-/-mice were enriched for genes associated with energy metabolism and diabetes;Phospho1both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adultPhospho1-/-mice. However, the decreased serum choline levels inPhospho1-/-mice were normalized by feeding a 2% choline rich diet resulting in a normalization in insulin sensitivity and fat mass. This study identifies PHOSPHO1 as a potential therapeutic target for the treatment of o...

Research paper thumbnail of The Journal of Nutrition Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions Sodium Acetate Induces a Metabolic Alkalosis but Not the Increase in Fatty Acid Oxidation Observed Following Bicarbonate Ingestion in Humans 1,2

Journal of Nutrition

We conducted this study to quantify the oxidation of exogenous acetate and to determine the effec... more We conducted this study to quantify the oxidation of exogenous acetate and to determine the effect of increased acetate availability upon fat and carbohydrate utilization in humans at rest. Eight healthy volunteers (6 males and 2 females) completed 2 separate trials, 7 d apart in a single-blind, randomized, crossover design. On each occasion, respiratory gas and arterialized venous blood samples were taken before and during 180 min following consumption of a drink containing either sodium acetate (NaAc) or NaHCO 3 at a dose of 2 mmol/kg body mass. Labeled [1,2-13 C] NaAc was added to the NaAc drink to quantify acetate oxidation. Both sodium salts induced a mild metabolic alkalosis and increased energy expenditure (P , 0.05) to a similar magnitude. NaHCO 3 ingestion increased fat utilization from 587 6 83 kJ/180 min to 693 6 101 kJ/180 min (P ¼ 0.01) with no change in carbohydrate utilization. Following ingestion of NaAc, the amount of fat and carbohydrate utilized did not differ fro...

Research paper thumbnail of Determining Ischaemic Thresholds Through Our Understanding of Cellular Metabolism

Compartment Syndrome, 2019

Research paper thumbnail of IAC-04-GP 36 Neuromuscular and Hormonal Effects of a Single Session of Whole Body Vibration

Research paper thumbnail of Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle

The Journal of endocrinology, 2015

Skeletal muscle has the capacity to increase energy turnover by ∼1000 times its resting rate when... more Skeletal muscle has the capacity to increase energy turnover by ∼1000 times its resting rate when contracting at the maximum force/power output. Since ATP is not stored in any appreciable quantity, the muscle requires a coordinated metabolic response to maintain an adequate supply of ATP to sustain contractile activity. The integration of intracellular metabolic pathways is dependent upon the cross-bridge cycling rate of myosin and actin, substrate availability and the accumulation of metabolic byproducts, all of which can influence the maintenance of contractile activity or result in the onset of fatigue. In addition, the mobilisation of extracellular substrates is dependent upon the integration of both the autonomic nervous system and endocrine systems to coordinate an increase in both carbohydrate and fat availability. The current review examines the evidence for skeletal muscle to generate power over short and long durations and discusses the metabolic response to sustain these ...

Research paper thumbnail of Conference report: the importance of the gut microbiome and nutrition on health

Gut Microbiome, 2021

The Nutrition Society Spring Conference (28–29 March 2021) focussed on the gut microbiome and hea... more The Nutrition Society Spring Conference (28–29 March 2021) focussed on the gut microbiome and health that was divided across three separate but inter-related areas from the impact of nutrition on the gut microbiome, the cause and effect of nutrition and health on the gut microbiome to the interaction between pathogens and gut microbiota. The program was supported by two plenary lectures, the first discussed the computational methods commonly employed to examine gut microbiota and the concluding lecture presented the interaction between gut microbiome, nutrition and health in older populations.

Research paper thumbnail of Understanding the interplay between the gut microbiome, nutrition and health

Proceedings of the Nutrition Society, 2021

The Spring Conference 2021 focused on the theme of the gut microbiome and health that was divided... more The Spring Conference 2021 focused on the theme of the gut microbiome and health that was divided across three separate but inter-related areas from the impact of nutrition on the gut microbiome, the cause and effect of nutrition and health on the gut microbiome to the interaction between pathogens and gut microbiota. The programme was supported by two plenary lectures, the first discussed the computational methods commonly employed to examine gut microbiota and the concluding lecture presented the interaction between the gut microbiome, nutrition and health in older populations. This short report provides a summary and highlights of the conference.

Research paper thumbnail of The Effect of Sodium Acetate Ingestion on the Metabolic Response to Prolonged Moderate-Intensity Exercise in Humans

International Journal of Sport Nutrition and Exercise Metabolism, 2013

At rest, administration of the short-chain fatty acid acetate suppresses fat oxidation without af... more At rest, administration of the short-chain fatty acid acetate suppresses fat oxidation without affecting carbohydrate utilization. The combined effect of increased acetate availability and exercise on substrate utilization is, however, unclear. With local ethics approval, we studied the effect of ingesting either sodium acetate (NaAc) or sodium bicarbonate (NaHCO3) at a dose of 4 mmol·kg-1 body mass 90 min before completing 120 min of exercise at 50% VO2peak. Six healthy young men completed the trials after an overnight fast and ingested the sodium salts in randomized order. As expected NaAc ingestion decreased resting fat oxidation (mean ± SD; 0.09 ± 0.02 vs. 0.07 ± 0.02 g·min-1 pre- and post-ingestion respectively, p < .05) with no effect upon carbohydrate utilization. In contrast, NaHCO3 ingestion had no effect on substrate utilization at rest. In response to exercise, fat and CHO oxidation increased in both trials, but fat oxidation was lower (0.16 ± 0.10 vs. 0.29 ± 0.11 g·mi...

Research paper thumbnail of Sodium acetate decreases phosphorylation of hormone sensitive lipase in isoproterenol-stimulated 3T3-L1 mature adipocytes

Adipocyte, 2014

Lipolysis, the process of hydrolysis of stored triacylglycerol into glycerol and non-esterified f... more Lipolysis, the process of hydrolysis of stored triacylglycerol into glycerol and non-esterified fatty acids (NEFA), is reported to be reduced by short chain fatty acids (SCFA) but the mechanism of this inhibition is poorly understood. The aim of this study was to measure the phosphorylation at serine residue 563 of hormone sensitive lipase with and without exposure to sodium acetate. Using the 3T3-L1 cell line, we identified that stimulating the cells with isoproterenol increased phosphorylated hormone sensitive lipase (pHSL) expression by 60% compared with the basal state. In the presence of the SCFA acetate in stimulated cells, pHSL decreased by 15% compared with stimulated cells alone. These results were mirrored by the NEFA release from stimulated cells that had significantly decreased in the presence of sodium acetate after 60 min (from 0.53 µmol mg(-1) protein to 0.41 µmol mg(-1) protein, respectively, P = 0.004); and 180 min (1.73 µmol mg(-1) protein to 1.13 µmol mg(-1) prote...

Research paper thumbnail of Effect of muscle temperature on rate of oxygen uptake during exercise in humans at different contraction frequencies

Journal of Experimental Biology, 2002

The effect of elevated human muscle temperature on energy turnover was investigated during cyclin... more The effect of elevated human muscle temperature on energy turnover was investigated during cycling exercise (at 85 % of (VO(2)max)) at a contraction frequency of 60 revs min(-1). Muscle temperature was passively elevated prior to exercise by immersion of the legs in a hot water bath (42 degrees C). During exercise at this low pedalling rate, total energy turnover was higher (P<0.05) when muscle temperature was elevated compared with normal temperature (70.4+/-3.7 versus 66.9+/-2.4 kJ min(-1), respectively). Estimated net mechanical efficiency was found to be lower when muscle temperature was elevated. A second experiment was conducted in which the effect of elevated human muscle temperature on energy turnover was investigated during cycling exercise (at 85 % of (VO(2)max)) at a contraction frequency of 120 revs min(-1). Under the conditions of a high pedalling frequency, an elevated muscle temperature resulted in a lower energy turnover (P<0.05) compared with the normal muscle...

Research paper thumbnail of Contrasting effects of heat stress on neuromuscular performance

Research paper thumbnail of Remote sensing of blood oxygenation using red-eye pupil reflection

Physiological Measurement

Research paper thumbnail of Meeting Preview: Physiology 2019

Research paper thumbnail of Physiological, Perceptual and Performance Responses Associated With Self-Selected Versus Standardized Recovery Periods During a Repeated Sprint Protocol in Elite Youth Football Players: A Preliminary Study

Pediatric exercise science, Jan 4, 2017

To examine the physiological and perceptual responses of youth footballers to a repeated sprint p... more To examine the physiological and perceptual responses of youth footballers to a repeated sprint protocol employing standardized and self-selected recovery. Eleven male participants (13.7 ± 1.1 years) performed a repeated sprint assessment comprising 10 x 30 m efforts. Employing a randomized crossover design, repeated sprints were performed using 30 s and self-selected recovery periods. Heart rate was monitored continuously with ratings of perceived exertion (RPE) and lower body muscle power measured 2 min after the final sprint. The concentration of blood lactate was measured at 2, 5 and 7 minutes post sprinting. Magnitude of effects were reported using effect size (ES) statistics ± 90% confidence interval and percentage differences. Differences between trials were examined using paired student t-tests (p < 0.05). Self-selected recovery resulted in most likely shorter recovery times (57.7%; ES 1.55 ± 0.5; p < 0.01), a most likely increase in percentage decrement (65%; ES 0.36 ...

Research paper thumbnail of Effect of muscle temperature on rate of oxygen uptake during exercise in humans at different contraction frequencies

The Journal of Experimental Biology, Apr 1, 2002

Research paper thumbnail of Effect of muscle temperature on skeletal muscle energy turnover during dynamic knee extensor exercise in humans

Research paper thumbnail of Effects of prior heavy exercise on V(over dot)O-2 kinetics during heavy exercise are related to changes in muscle activity

Research paper thumbnail of The effect of sodium acetate ingestion on acid-base balance and resting metabolism in man

Research paper thumbnail of Molecular mechanisms underlying the plasticity of muscle contractile properties with temperature acclimation in the marine fish Myoxocephalus scorpius

Journal of Experimental Biology

Research paper thumbnail of PHOSPHO1 is a skeletal regulator of insulin resistance and obesity

BMC Biology, 2020

Background The classical functions of the skeleton encompass locomotion, protection and mineral h... more Background The classical functions of the skeleton encompass locomotion, protection and mineral homeostasis. However, cell-specific gene deletions in the mouse and human genetic studies have identified the skeleton as a key endocrine regulator of metabolism. The bone-specific phosphatase, Phosphatase, Orphan 1 (PHOSPHO1), which is indispensable for bone mineralisation, has been recently implicated in the regulation of energy metabolism in humans, but its role in systemic metabolism remains unclear. Here, we probe the mechanism underlying metabolic regulation by analysing Phospho1 mutant mice. Results Phospho1−/− mice exhibited improved basal glucose homeostasis and resisted high-fat-diet-induced weight gain and diabetes. The metabolic protection in Phospho1−/− mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated from Phospho1−/− mice were enriched for genes associated with energy metabolism and diabetes; Phospho1 both directly and indirectly inte...

Research paper thumbnail of PHOSPHO1, a novel skeletal regulator of insulin resistance and obesity

The skeleton is recognised as a key endocrine regulator of metabolism. Here we show that mice lac... more The skeleton is recognised as a key endocrine regulator of metabolism. Here we show that mice lacking the bone mineralization enzyme PHOSPHO1 (Phospho1-/-) exhibited improved basal glucose homeostasis and resisted high-fat-diet induced weight gain and diabetes. The metabolic protection inPhospho1-/-mice was manifested in the absence of altered levels of osteocalcin. Osteoblasts isolated fromPhospho1-/-mice were enriched for genes associated with energy metabolism and diabetes;Phospho1both directly and indirectly interacted with genes associated with glucose transport and insulin receptor signalling. Canonical thermogenesis via brown adipose tissue did not underlie the metabolic protection observed in adultPhospho1-/-mice. However, the decreased serum choline levels inPhospho1-/-mice were normalized by feeding a 2% choline rich diet resulting in a normalization in insulin sensitivity and fat mass. This study identifies PHOSPHO1 as a potential therapeutic target for the treatment of o...

Research paper thumbnail of The Journal of Nutrition Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions Sodium Acetate Induces a Metabolic Alkalosis but Not the Increase in Fatty Acid Oxidation Observed Following Bicarbonate Ingestion in Humans 1,2

Journal of Nutrition

We conducted this study to quantify the oxidation of exogenous acetate and to determine the effec... more We conducted this study to quantify the oxidation of exogenous acetate and to determine the effect of increased acetate availability upon fat and carbohydrate utilization in humans at rest. Eight healthy volunteers (6 males and 2 females) completed 2 separate trials, 7 d apart in a single-blind, randomized, crossover design. On each occasion, respiratory gas and arterialized venous blood samples were taken before and during 180 min following consumption of a drink containing either sodium acetate (NaAc) or NaHCO 3 at a dose of 2 mmol/kg body mass. Labeled [1,2-13 C] NaAc was added to the NaAc drink to quantify acetate oxidation. Both sodium salts induced a mild metabolic alkalosis and increased energy expenditure (P , 0.05) to a similar magnitude. NaHCO 3 ingestion increased fat utilization from 587 6 83 kJ/180 min to 693 6 101 kJ/180 min (P ¼ 0.01) with no change in carbohydrate utilization. Following ingestion of NaAc, the amount of fat and carbohydrate utilized did not differ fro...

Research paper thumbnail of Determining Ischaemic Thresholds Through Our Understanding of Cellular Metabolism

Compartment Syndrome, 2019

Research paper thumbnail of IAC-04-GP 36 Neuromuscular and Hormonal Effects of a Single Session of Whole Body Vibration

Research paper thumbnail of Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle

The Journal of endocrinology, 2015

Skeletal muscle has the capacity to increase energy turnover by ∼1000 times its resting rate when... more Skeletal muscle has the capacity to increase energy turnover by ∼1000 times its resting rate when contracting at the maximum force/power output. Since ATP is not stored in any appreciable quantity, the muscle requires a coordinated metabolic response to maintain an adequate supply of ATP to sustain contractile activity. The integration of intracellular metabolic pathways is dependent upon the cross-bridge cycling rate of myosin and actin, substrate availability and the accumulation of metabolic byproducts, all of which can influence the maintenance of contractile activity or result in the onset of fatigue. In addition, the mobilisation of extracellular substrates is dependent upon the integration of both the autonomic nervous system and endocrine systems to coordinate an increase in both carbohydrate and fat availability. The current review examines the evidence for skeletal muscle to generate power over short and long durations and discusses the metabolic response to sustain these ...

Research paper thumbnail of Conference report: the importance of the gut microbiome and nutrition on health

Gut Microbiome, 2021

The Nutrition Society Spring Conference (28–29 March 2021) focussed on the gut microbiome and hea... more The Nutrition Society Spring Conference (28–29 March 2021) focussed on the gut microbiome and health that was divided across three separate but inter-related areas from the impact of nutrition on the gut microbiome, the cause and effect of nutrition and health on the gut microbiome to the interaction between pathogens and gut microbiota. The program was supported by two plenary lectures, the first discussed the computational methods commonly employed to examine gut microbiota and the concluding lecture presented the interaction between gut microbiome, nutrition and health in older populations.

Research paper thumbnail of Understanding the interplay between the gut microbiome, nutrition and health

Proceedings of the Nutrition Society, 2021

The Spring Conference 2021 focused on the theme of the gut microbiome and health that was divided... more The Spring Conference 2021 focused on the theme of the gut microbiome and health that was divided across three separate but inter-related areas from the impact of nutrition on the gut microbiome, the cause and effect of nutrition and health on the gut microbiome to the interaction between pathogens and gut microbiota. The programme was supported by two plenary lectures, the first discussed the computational methods commonly employed to examine gut microbiota and the concluding lecture presented the interaction between the gut microbiome, nutrition and health in older populations. This short report provides a summary and highlights of the conference.

Research paper thumbnail of The Effect of Sodium Acetate Ingestion on the Metabolic Response to Prolonged Moderate-Intensity Exercise in Humans

International Journal of Sport Nutrition and Exercise Metabolism, 2013

At rest, administration of the short-chain fatty acid acetate suppresses fat oxidation without af... more At rest, administration of the short-chain fatty acid acetate suppresses fat oxidation without affecting carbohydrate utilization. The combined effect of increased acetate availability and exercise on substrate utilization is, however, unclear. With local ethics approval, we studied the effect of ingesting either sodium acetate (NaAc) or sodium bicarbonate (NaHCO3) at a dose of 4 mmol·kg-1 body mass 90 min before completing 120 min of exercise at 50% VO2peak. Six healthy young men completed the trials after an overnight fast and ingested the sodium salts in randomized order. As expected NaAc ingestion decreased resting fat oxidation (mean ± SD; 0.09 ± 0.02 vs. 0.07 ± 0.02 g·min-1 pre- and post-ingestion respectively, p < .05) with no effect upon carbohydrate utilization. In contrast, NaHCO3 ingestion had no effect on substrate utilization at rest. In response to exercise, fat and CHO oxidation increased in both trials, but fat oxidation was lower (0.16 ± 0.10 vs. 0.29 ± 0.11 g·mi...

Research paper thumbnail of Sodium acetate decreases phosphorylation of hormone sensitive lipase in isoproterenol-stimulated 3T3-L1 mature adipocytes

Adipocyte, 2014

Lipolysis, the process of hydrolysis of stored triacylglycerol into glycerol and non-esterified f... more Lipolysis, the process of hydrolysis of stored triacylglycerol into glycerol and non-esterified fatty acids (NEFA), is reported to be reduced by short chain fatty acids (SCFA) but the mechanism of this inhibition is poorly understood. The aim of this study was to measure the phosphorylation at serine residue 563 of hormone sensitive lipase with and without exposure to sodium acetate. Using the 3T3-L1 cell line, we identified that stimulating the cells with isoproterenol increased phosphorylated hormone sensitive lipase (pHSL) expression by 60% compared with the basal state. In the presence of the SCFA acetate in stimulated cells, pHSL decreased by 15% compared with stimulated cells alone. These results were mirrored by the NEFA release from stimulated cells that had significantly decreased in the presence of sodium acetate after 60 min (from 0.53 µmol mg(-1) protein to 0.41 µmol mg(-1) protein, respectively, P = 0.004); and 180 min (1.73 µmol mg(-1) protein to 1.13 µmol mg(-1) prote...

Research paper thumbnail of Effect of muscle temperature on rate of oxygen uptake during exercise in humans at different contraction frequencies

Journal of Experimental Biology, 2002

The effect of elevated human muscle temperature on energy turnover was investigated during cyclin... more The effect of elevated human muscle temperature on energy turnover was investigated during cycling exercise (at 85 % of (VO(2)max)) at a contraction frequency of 60 revs min(-1). Muscle temperature was passively elevated prior to exercise by immersion of the legs in a hot water bath (42 degrees C). During exercise at this low pedalling rate, total energy turnover was higher (P<0.05) when muscle temperature was elevated compared with normal temperature (70.4+/-3.7 versus 66.9+/-2.4 kJ min(-1), respectively). Estimated net mechanical efficiency was found to be lower when muscle temperature was elevated. A second experiment was conducted in which the effect of elevated human muscle temperature on energy turnover was investigated during cycling exercise (at 85 % of (VO(2)max)) at a contraction frequency of 120 revs min(-1). Under the conditions of a high pedalling frequency, an elevated muscle temperature resulted in a lower energy turnover (P<0.05) compared with the normal muscle...

Research paper thumbnail of Contrasting effects of heat stress on neuromuscular performance

Research paper thumbnail of Remote sensing of blood oxygenation using red-eye pupil reflection

Physiological Measurement

Research paper thumbnail of Meeting Preview: Physiology 2019

Research paper thumbnail of Physiological, Perceptual and Performance Responses Associated With Self-Selected Versus Standardized Recovery Periods During a Repeated Sprint Protocol in Elite Youth Football Players: A Preliminary Study

Pediatric exercise science, Jan 4, 2017

To examine the physiological and perceptual responses of youth footballers to a repeated sprint p... more To examine the physiological and perceptual responses of youth footballers to a repeated sprint protocol employing standardized and self-selected recovery. Eleven male participants (13.7 ± 1.1 years) performed a repeated sprint assessment comprising 10 x 30 m efforts. Employing a randomized crossover design, repeated sprints were performed using 30 s and self-selected recovery periods. Heart rate was monitored continuously with ratings of perceived exertion (RPE) and lower body muscle power measured 2 min after the final sprint. The concentration of blood lactate was measured at 2, 5 and 7 minutes post sprinting. Magnitude of effects were reported using effect size (ES) statistics ± 90% confidence interval and percentage differences. Differences between trials were examined using paired student t-tests (p < 0.05). Self-selected recovery resulted in most likely shorter recovery times (57.7%; ES 1.55 ± 0.5; p < 0.01), a most likely increase in percentage decrement (65%; ES 0.36 ...

Research paper thumbnail of Effect of muscle temperature on rate of oxygen uptake during exercise in humans at different contraction frequencies

The Journal of Experimental Biology, Apr 1, 2002

Research paper thumbnail of Effect of muscle temperature on skeletal muscle energy turnover during dynamic knee extensor exercise in humans

Research paper thumbnail of Effects of prior heavy exercise on V(over dot)O-2 kinetics during heavy exercise are related to changes in muscle activity

Research paper thumbnail of The effect of sodium acetate ingestion on acid-base balance and resting metabolism in man

Research paper thumbnail of Molecular mechanisms underlying the plasticity of muscle contractile properties with temperature acclimation in the marine fish Myoxocephalus scorpius

Journal of Experimental Biology