Genes and biochemical pathways in human skeletal muscle affecting resting energy expenditure and fuel partitioning

Genes influencing resting energy expenditure (REE) and respiratory quotient (RQ) represent candidate genes for obesity and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. We aim to explore the molecular basis for individual variation in REE and fuel partitioning as reflected by RQ. We performed microarray studies in human vastus lateralis muscle biopsies from 40 healthy subjects with measured REE and RQ values. We identified 2,392 and 1,115 genes significantly correlated with REE and RQ, respectively. Genes correlated with REE and RQ encompass a broad array of functions, including carbohydrate and lipid metabolism, gene expression, mitochondrial processes, and membrane transport. Microarray pathway analysis revealed that REE was positively correlated with upregulation of G protein-coupled receptor signaling (meet criteria/total genes: 65 of 283) involved in autonomic nervous system functions, including those receptors mediating adrenergic, dopamine, γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and serotonin action (meet criteria/total genes: 46 of 176). Reduced REE was associated with an increase in genes participating in ubiquitin-proteasome-dependent proteolytic pathways (58 of 232). Serine-type peptidase activity (9 of 76) was positively correlated with RQ, while genes involved in the protein phosphatase type 2A complex (4 of 9), mitochondrial function and cellular respiration (38 of 315), and unfolded protein binding (19 of 97) were associated with reduced RQ values and a preference for lipid fuel metabolism. Individual variations in whole body REE and RQ are regulated by differential expressions of specific genes and pathways intrinsic to skeletal muscle.

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Female rats selectively bred for high intrinsic aerobic fitness are protected from ovariectomy-associated metabolic dysfunction

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00401.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. R530-R542 ◽

Cited By ~ 34

Author(s):

Victoria J. Vieira-Potter ◽

Jaume Padilla ◽

Young-Min Park ◽

Rebecca J. Welly ◽

Rebecca J. Scroggins ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Energy Expenditure ◽

Aerobic Fitness ◽

Resting Energy Expenditure ◽

Female Rats ◽

Metabolic Dysfunction ◽

Spontaneous Physical Activity ◽

Resting Energy

Ovariectomized rodents model human menopause in that they rapidly gain weight, reduce spontaneous physical activity (SPA), and develop metabolic dysfunction, including insulin resistance. How contrasting aerobic fitness levels impacts ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats selectively bred for high and low intrinsic aerobic fitness [high-capacity runners (HCR) and low-capacity runners (LCR), respectively] were maintained under sedentary conditions for 39 wk. Midway through the observation period, OVX or sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR-OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before and 4 wk after surgery, while body composition via dual-energy X-ray absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and skeletal muscle phenotype, hepatic lipid content, insulin resistance via homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids were assessed at death. Remarkably, HCR were protected from OVX-associated increases in adiposity and insulin resistance, observed only in LCR. HCR rats were ∼30% smaller, had ∼70% greater spontaneous physical activity (SPA), consumed ∼10% more relative energy, had greater skeletal muscle proliferator-activated receptor coactivator 1-alpha, and ∼40% more BAT. OVX did not increase energy intake and reduced SPA to the same extent in both HCR and LCR. LCR were particularly affected by an OVX-associated reduction in resting energy expenditure and experienced a reduction in relative BAT; resting energy expenditure correlated positively with BAT across all animals ( r = 0.6; P < 0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic fitness protects against OVX-associated increases in adiposity and insulin resistance. The mechanism may involve preservation of resting energy expenditure.

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Whole body protein metabolism and resting energy expenditure in pregnant Gambian women

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.4.e624 ◽

1992 ◽

Vol 263 (4) ◽

pp. E624-E631 ◽

Cited By ~ 2

Author(s):

L. Willommet ◽

Y. Schutz ◽

R. Whitehead ◽

E. Jequier ◽

E. B. Fern

Keyword(s):

Protein Synthesis ◽

Energy Expenditure ◽

Protein Metabolism ◽

Resting Energy Expenditure ◽

First Trimester ◽

Significant Rise ◽

Whole Body ◽

Body Protein ◽

Fed State ◽

Resting Energy

Whole body protein metabolism and resting energy expenditure (REE) were measured at 11, 23, and 33 wk of pregnancy in nine pregnant (not malnourished) Gambian women and in eight matched nonpregnant nonlactating (NPNL) matched controls. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotope enrichment of urinary urea and ammonia during a period of 9 h after a single oral dose of [15N]glycine. At regular intervals, REE was measured by indirect calorimetry (hood system). Based on the arithmetic end-product average of values obtained with urea and ammonia, a significant increase in whole body protein synthesis was observed during the second trimester (5.8 +/- 0.4 g.kg-1.day-1) relative to values obtained both for the NPNL controls (4.5 +/- 0.3 g.kg-1.day-1) and those during the first trimester (4.7 +/- 0.3 g.kg-1.day-1). There was a significant rise in REE during the third trimester both in the preprandial and postprandial states. No correlation was found between REE after meal ingestion and the rate of whole body protein synthesis.

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Accuracy and reliability of a portable indirect calorimeter compared to whole-body indirect calorimetry for measuring resting energy expenditure

Clinical Nutrition ESPEN ◽

10.1016/j.clnesp.2020.07.017 ◽

2020 ◽

Vol 39 ◽

pp. 67-73 ◽

Cited By ~ 1

Author(s):

Sarah A. Purcell ◽

Carlene Johnson-Stoklossa ◽

Jenneffer Rayane Braga Tibaes ◽

Alena Frankish ◽

Sarah A. Elliott ◽

...

Keyword(s):

Energy Expenditure ◽

Indirect Calorimetry ◽

Resting Energy Expenditure ◽

Whole Body ◽

Resting Energy

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Mitochondrial Function and Insulin Resistance in Overweight and Normal-Weight Children

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-1590 ◽

2009 ◽

Vol 94 (12) ◽

pp. 4923-4930 ◽

Cited By ~ 38

Author(s):

Amy Fleischman ◽

Matthew Kron ◽

David M. Systrom ◽

Mirko Hrovat ◽

Steven K. Grinspoon

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Energy Expenditure ◽

Mitochondrial Function ◽

Resting Energy Expenditure ◽

Normal Weight ◽

Metabolic Phenotype ◽

Overweight Children ◽

Insulin Resistant ◽

Resting Energy

Background: Obesity has become an epidemic in children, associated with an increase in insulin resistance and metabolic dysfunction. Mitochondrial function is known to be an important determinant of glucose metabolism in adults. However, little is known about the relationship between mitochondrial function and obesity, insulin resistance, energy expenditure, and pubertal development in children. Methods: Seventy-four participants, 37 overweight (≥85th percentile body mass index for age and sex) and 37 normal-weight (<85th percentile) without personal or family history of diabetes mellitus were enrolled. Subjects were evaluated with an oral glucose tolerance test, metabolic markers, resting energy expenditure, Tanner staging, and 31P magnetic resonance spectroscopy of skeletal muscle for mitochondrial function. Results: Overweight and normal-weight children showed no difference in muscle ATP synthesis [phosphocreatine (PCr) recovery after exercise] (32.4 ± 2.3 vs. 34.1 ± 2.1, P = 0.58). However, insulin-resistant children had significantly prolonged PCr recovery when compared with insulin-sensitive children, by homeostasis model assessment for insulin resistance quartile (ANOVA, P = 0.04). Similarly, insulin-resistant overweight children had PCr recovery that was prolonged compared with insulin-sensitive overweight children (P = 0.01). PCr recovery was negatively correlated with resting energy expenditure in multivariate modeling (P = 0.03). Mitochondrial function worsened during mid-puberty in association with insulin resistance. Conclusion: Reduced skeletal muscle mitochondrial oxidative phosphorylation, assessed by PCr recovery, is associated with insulin resistance and an altered metabolic phenotype in children. Normal mitochondrial function may be associated with a healthier metabolic phenotype in overweight children. Further studies are needed to investigate the long-term physiological consequences and potential treatment strategies targeting children with reduced mitochondrial function.

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Leucine kinetics in endurance-trained humans

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.1.1 ◽

1990 ◽

Vol 69 (1) ◽

pp. 1-6 ◽

Cited By ~ 28

Author(s):

L. S. Lamont ◽

D. G. Patel ◽

S. C. Kalhan

Keyword(s):

Energy Expenditure ◽

Protein Turnover ◽

Resting Energy Expenditure ◽

Whole Body ◽

Body Protein ◽

Energy Expenditures ◽

Leucine Kinetics ◽

Constant Rate ◽

Tracer Dilution ◽

Resting Energy

This study compared whole-body leucine kinetics in endurance-trained (TRN) and sedentary (SED) control subjects. Eleven men and women (6 TRN, 5 SED) underwent a 6-h primed, constant-rate infusion of L-[1-13C]leucine. Leucine turnover and oxidation were measured using tracer dilution and by measuring 13C enrichment of expired CO2 combined with respiratory calorimetry. Whole-body leucine turnover was greater in the TRN subjects (P less than 0.004; TRN 98.3 +/- 5.0, SED 75.3 +/- 4.2 mumol.kg-1.h-1; mean +/- SE), but there was no difference between groups in leucine oxidation (TRN 13.1 +/- 0.97, SED 11.5 +/- 0.48 mumol.kg-1.h-1). Thus more leucine turnover was available for nonoxidative utilization. In addition, the TRN subjects had higher resting energy expenditures compared with the SED group, and when all subjects were included in the analysis, there was a significant correlation between energy expenditure and protein turnover (n = 11, R = 0.61, P = 0.05). Therefore the heightened resting energy expenditure in the TRN subjects may be accounted for by an increased whole-body protein turnover. These results suggest that endurance training results in increased leucine and/or protein turnover, which may contribute to the increased resting energy expenditure observed in these subjects.

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Skeletal muscle oxidative function in vivo and ex vivo in athletes with marked hypertrophy from resistance training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00883.2012 ◽

2013 ◽

Vol 114 (11) ◽

pp. 1527-1535 ◽

Cited By ~ 31

Author(s):

Desy Salvadego ◽

Rossana Domenis ◽

Stefano Lazzer ◽

Simone Porcelli ◽

Jörn Rittweger ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Training ◽

Muscle Mass ◽

Body Mass ◽

Mitochondrial Respiration ◽

Ex Vivo ◽

Vastus Lateralis ◽

Whole Body ◽

Vastus Lateralis Muscle ◽

Oxidative Function

Oxidative function during exercise was evaluated in 11 young athletes with marked skeletal muscle hypertrophy induced by long-term resistance training (RTA; body mass 102.6 ± 7.3 kg, mean ± SD) and 11 controls (CTRL; body mass 77.8 ± 6.0 kg). Pulmonary O2 uptake (V̇o2) and vastus lateralis muscle fractional O2 extraction (by near-infrared spectroscopy) were determined during an incremental cycle ergometer (CE) and one-leg knee-extension (KE) exercise. Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers obtained by biopsy. Quadriceps femoris muscle cross-sectional area, volume (determined by magnetic resonance imaging), and strength were greater in RTA vs. CTRL (by ∼40%, ∼33%, and ∼20%, respectively). V̇o2peak during CE was higher in RTA vs. CTRL (4.05 ± 0.64 vs. 3.56 ± 0.30 l/min); no difference between groups was observed during KE. The O2 cost of CE exercise was not different between groups. When divided per muscle mass (for CE) or quadriceps muscle mass (for KE), V̇o2 peak was lower (by 15–20%) in RTA vs. CTRL. Vastus lateralis fractional O2 extraction was lower in RTA vs. CTRL at all work rates, during both CE and KE. RTA had higher ADP-stimulated mitochondrial respiration (56.7 ± 23.7 pmol O2·s−1·mg−1 ww) vs. CTRL (35.7 ± 10.2 pmol O2·s−1·mg−1 ww) and a tighter coupling of oxidative phosphorylation. In RTA, the greater muscle mass and maximal force and the enhanced mitochondrial respiration seem to compensate for the hypertrophy-induced impaired peripheral O2 diffusion. The net results are an enhanced whole body oxidative function at peak exercise and unchanged efficiency and O2 cost at submaximal exercise, despite a much greater body mass.

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Energy expenditure and substrate metabolism measured by 24 h whole-body calorimetry in patients receiving cyclic and continuous total parenteral nutrition

Clinical Science ◽

10.1042/cs0800571 ◽

1991 ◽

Vol 80 (6) ◽

pp. 571-582 ◽

Cited By ~ 17

Author(s):

E. Pullicino ◽

G. R. Goldberg ◽

M. Elia

Keyword(s):

Energy Expenditure ◽

Parenteral Nutrition ◽

Metabolic Rate ◽

Total Parenteral Nutrition ◽

Basal Metabolic Rate ◽

Resting Energy Expenditure ◽

Whole Body ◽

Diet Induced Thermogenesis ◽

Activity Energy ◽

Resting Energy

1. Twenty-four hour energy expenditure and its components, i.e. ‘basal metabolic rate', activity energy expenditure and diet-induced thermogenesis were measured, using continuous whole-body indirect calorimetry, in patients receiving total parenteral nutrition while in remission from Crohn's disease (weight 51.9 ± 9.9 kg, body mass index 19.2 ± 2.0 kg/m2). 2. Total parenteral nutrition was infused continuously over 24 h in four subjects and cyclically, between 22.00 and 10.00 hours, in eight subjects. Twenty-four hour energy expenditure (6.83 ± 1.10 MJ/24 h) was lower than total energy intake (10.09 ± 1.63 MJ/24 h), resulting in a positive energy balance (3.26 ± 1.42 MJ) in all subjects. Repeated measurements of resting energy expenditure in the continuously fed subjects (5.82 ± 1.11 MJ/24 h) did not change significantly at different times of day (coefficient of variation 2.2–6.6%). In contrast, in cyclically fed subjects, resting energy expenditure was 24.2 ± 9.0% higher towards the end of the 12 h feeding period than the ‘basal metabolic rate', which was measured just before the start of the feeding period. 3. Diet-induced thermogenesis, calculated as the increment in resting energy expenditure above ‘basal metabolic rate’ over the 24 h period (adjusted for the reduction in energy expenditure during sleep), was found to be 0.60 ± 0.29 MJ or 6.1 ± 3.1% of the energy intake. 4. The energy cost of activity (activity energy expenditure) in the continuously fed patients, calculated as the difference between 24 h energy expenditure and the integrated 24 h measurements of resting energy expenditure, was 0.88 ± 0.53 MJ, i.e. 12.9 ± 5.9% of the 24 h energy expenditure. 5. The non-protein nonglycerol respiratory quotient exceeded 1.0 for varying periods of time (0.5–17 h) in 11 subjects, indicating net lipogenesis from carbohydrate. 6. The results demonstrate favourable rates of deposition, during intravenous feeding, of both energy and nitrogen over a 24 h period in patients recovering from an episode of Crohn's disease. The efficacy of these commonly used total parenteral nutrition regimens in these patients is related to three features that are absent in normal healthy individuals, namely a low basal metabolic rate, a low activity-related energy expenditure and prolonged periods of lipogenesis from carbohydrate.

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New records in aerobic power among octogenarian lifelong endurance athletes

Journal of Applied Physiology ◽

10.1152/japplphysiol.01107.2012 ◽

2013 ◽

Vol 114 (1) ◽

pp. 3-10 ◽

Cited By ~ 53

Author(s):

Scott Trappe ◽

Erik Hayes ◽

Andrew Galpin ◽

Leonard Kaminsky ◽

Bozena Jemiolo ◽

...

Keyword(s):

Skeletal Muscle ◽

Aerobic Capacity ◽

Citrate Synthase ◽

Vastus Lateralis ◽

Endurance Athletes ◽

Whole Body ◽

Oxidative Enzymes ◽

Vastus Lateralis Muscle ◽

Peroxisome Proliferator ◽

Mrna Targets

We examined whole body aerobic capacity and myocellular markers of oxidative metabolism in lifelong endurance athletes [ n = 9, 81 ± 1 yr, 68 ± 3 kg, body mass index (BMI) = 23 ± 1 kg/m2] and age-matched, healthy, untrained men ( n = 6; 82 ± 1 y, 77 ± 5 kg, BMI = 26 ± 1 kg/m2). The endurance athletes were cross-country skiers, including a former Olympic champion and several national/regional champions, with a history of aerobic exercise and participation in endurance events throughout their lives. Each subject performed a maximal cycle test to assess aerobic capacity (V̇o2max). Subjects had a resting vastus lateralis muscle biopsy to assess oxidative enzymes (citrate synthase and βHAD) and molecular (mRNA) targets associated with mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam)]. The octogenarian athletes had a higher ( P < 0.05) absolute (2.6 ± 0.1 vs. 1.6 ± 0.1 l/min) and relative (38 ± 1 vs. 21 ± 1 ml·kg−1·min−1) V̇o2max, ventilation (79 ± 3 vs. 64 ± 7 l/min), heart rate (160 ± 5 vs. 146 ± 8 beats per minute), and final workload (182 ± 4 vs. 131 ± 14 W). Skeletal muscle oxidative enzymes were 54% (citrate synthase) and 42% (βHAD) higher ( P < 0.05) in the octogenarian athletes. Likewise, basal PGC-1α and Tfam mRNA were 135% and 80% greater ( P < 0.05) in the octogenarian athletes. To our knowledge, the V̇o2max of the lifelong endurance athletes is the highest recorded in humans >80 yr of age and comparable to nonendurance trained men 40 years younger. The superior cardiovascular and skeletal muscle health profile of the octogenarian athletes provides a large functional reserve above the aerobic frailty threshold and is associated with lower risk for disability and mortality.

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