Acetylcarnitine is an essential metabolite for maintaining metabolic flexibility and glucose homeostasis. The in vivo behavior of muscle acetylcarnitine content during exercise has not been shown ...with magnetic resonance spectroscopy. Therefore, this study aimed to explore the behavior of skeletal muscle acetylcarnitine during rest, plantar flexion exercise, and recovery in the human gastrocnemius muscle under aerobic conditions. Ten lean volunteers and nine overweight volunteers participated in the study. A 7 T whole-body MR system with a double-tuned surface coil was used to acquire spectra from the gastrocnemius medialis. An MR-compatible ergometer was used for the plantar flexion exercise. Semi-LASER-localized 1H MR spectra and slab-localized 31P MR spectra were acquired simultaneously in one interleaved exercise/recovery session. The time-resolved interleaved 1H/31P MRS acquisition yielded excellent data quality. A between-group difference in acetylcarnitine metabolism over time was detected. Significantly slower τPCr recovery, τPCr on-kinetics, and lower Qmax in the overweight group, compared to the lean group was found. Linear relations between τPCr on-kinetics, τPCr recovery, VO2max and acetylcarnitine content were identified. In conclusion, we are the first to show in vivo changes of skeletal muscle acetylcarnitine during acute exercise and immediate exercise recovery with a submaximal aerobic workload using interleaved 1H/31P MRS at 7 T.
Aging is associated with changes in muscle energy metabolism. Proton (
H) and phosphorous (
P) magnetic resonance spectroscopy (MRS) has been successfully applied for non-invasive investigation of ...skeletal muscle metabolism. The aim of this study was to detect differences in adenosine triphosphate (ATP) production in the aging muscle by
P-MRS and to identify potential changes associated with buffer capacity of muscle carnosine by
H-MRS.
Fifteen young and nineteen elderly volunteers were examined.
H and
P-MRS spectra were acquired at high field (7T). The investigation included carnosine quantification using
H-MRS and resting and dynamic
P-MRS, both including saturation transfer measurements of phosphocreatine (PCr), and inorganic phosphate (Pi)-to-ATP metabolic fluxes.
Elderly volunteers had higher time constant of PCr recovery (τ
) in comparison to the young volunteers. Exercise was connected with significant decrease in PCr-to-ATP flux in both groups. Moreover, PCr-to-ATP flux was significantly higher in young compared to elderly both at rest and during exercise. Similarly, an increment of Pi-to-ATP flux with exercise was found in both groups but the intergroup difference was only observed during exercise. Elderly had lower muscle carnosine concentration and lower postexercise pH. A strong increase in phosphomonoester (PME) concentration was observed with exercise in elderly, and a faster Pi:PCr kinetics was found in young volunteers compared to elderly during the recovery period.
Observations of a massive increment of PME concentration together with high Pi-to-ATP flux during exercise in seniors refer to decreased ability of the muscle to meet the metabolic requirements of exercise and thus a limited ability of seniors to effectively support the exercise load.
Brain-derived neurotrophic factor (BDNF) participates in orchestrating the adaptive response to exercise. However, the importance of transient changes in circulating BDNF for eliciting whole-body and ...skeletal muscle exercise benefits in humans remains relatively unexplored. Here, we investigated effects of acute aerobic exercise and 3-month aerobic-strength training on serum, plasma and skeletal muscle BDNF in twenty-two sedentary older individuals (69.0 ± 8.0 yrs., 9 M/13F). BDNF response to acute exercise was additionally evaluated in young trained individuals (25.1 ± 2.1 yrs., 3 M/5F). Acute aerobic exercise transiently increased serum BDNF in sedentary (16%, p = .007) but not in trained elderly or young individuals. Resting serum or plasma BDNF was not regulated by exercise training in the elderly. However, subtle training-related changes of serum BDNF positively correlated with improvements in walking speed (R = 0.59, p = .005), muscle mass (R = 0.43, p = .04) and cognitive performance (R = 0.41, p = .05) and negatively with changes in body fat (R = -0.43, p = .04) and triglyceridemia (R = -0.53, p = .01). Individuals who increased muscle BDNF protein in response to 3-month training (responders) displayed stronger acute exercise-induced increase in serum BDNF than non-responders (p = .006). In addition, muscle BDNF protein content positively correlated with type II-to-type I muscle fiber ratio (R = 0.587, p = .008) and with the rate of post-exercise muscle ATP re-synthesis (R = 0.703, p = .005). Contrary to serum, acute aerobic exercise resulted in a decline of plasma BDNF 1 h post-exercise in both elderly-trained (−34%, p = .002) and young-trained individuals (−48%, p = .034). Acute circulating BDNF regulation by exercise was dependent on the level of physical fitness and correlated with training-induced improvements in metabolic and cognitive functions. Our observations provide an indirect evidence that distinct exercise-induced changes in serum and plasma BDNF as well as training-related increase in muscle BDNF protein, paralleled by improvements in muscle and whole-body clinical phenotypes, are involved in the coordinated adaptive response to exercise in humans.
•Acute exercise increases serum BDNF in the sedentary elderly and the response is blunted by aerobic-strength training.•Plasma BDNF is reduced 1 h post-exercise in exercise-trained elderly & young individuals, but not in sedentary seniors.•Training effect on serum BDNF is linked to improved walking speed, muscle mass & cognition and to lower body fat.•Training-induced increase in muscle BDNF protein parallel adaptive changes in muscle structure, function & metabolism.
The influence of endurance training on skeletal muscle metabolism can currently be studied only by invasive sampling or through a few related parameters that are investigated by either proton (
H) or ...phosphorus (
P) magnetic resonance spectroscopy (MRS). The aim of this study was to compare the metabolic differences between endurance-trained triathletes and healthy volunteers using multi-parametric data acquired by both,
P- and
H-MRS, at ultra-high field (7T) in a single experimental protocol. This study also aimed to determine the interrelations between these MRS-derived metabolic parameters.
Thirteen male triathletes and ten active male volunteers participated in the study. Proton MRS data from the vastus lateralis yielded concentrations of acetylcarnitine, carnosine, and intramyocellular lipids (IMCL). For the measurement of phosphodiesters (PDEs), inorganic phosphate (Pi), phosphocreatine (PCr), and maximal oxidative capacity (Q
) phosphorus MRS data were acquired at rest, during 6 min of submaximal exercise and following immediate recovery.
The triathletes exhibited significantly higher IMCL levels, higher initial rate of PCr resynthesis (V
) during the recovery period, a shorter PCr recovery time constant (τ
), and higher Q
. Multivariate stepwise regression analysis identified PDE as the strongest independent predictor of whole-body maximal oxygen uptake (VO
).
In conclusion, we cannot suggest a single MRS-based parameter as an exclusive biomarker of muscular fitness and training status. There is, rather, a combination of different parameters, assessable during a single multi-nuclear MRS session that could be useful for further cross-sectional and/or focused interventional studies on skeletal muscle fitness and training effects.
Background
Previous in vivo proton MR spectroscopy (MRS) studies have demonstrated the possibility of quantifying amide groups of conjugated bile acids (NHCBA), olefinic lipids and cholesterol (OLC), ...choline‐containing phospholipids (CCPLs), taurine and glycine conjugated bile acids (TCBA, GCBA), methylene group of lipids (ML), and methyl groups of bile acids, lipids, and cholesterol (BALC1.0, BALC0.9, and TBAC) in the gallbladder, which may be useful for the study of cholestatic diseases and cholangiopathies. However, these studies were performed at 1.5T and 3T, and higher magnetic fields may offer improved spectral resolution and signal intensity.
Purpose
To develop a method for gallbladder MRS at 7T.
Study Type
Retrospective, technical development.
Population
Ten healthy subjects (five males and five females), two patients with primary biliary cholangitis (PBC) (one male and one female), and one patient with primary sclerosing cholangitis (PSC) (female).
Field Strength/Sequence
Free‐breathing single‐voxel MRS with a modified stimulated echo acquisition mode (STEAM) sequence at 7T.
Assessment
Postprocessing was based on the T2 relaxation of water in the gallbladder and in the liver. Concentrations of biliary components were calculated using water signal. All data were corrected for T2 relaxation times measured in healthy subjects.
Statistical Tests
The range of T2 relaxation time and concentration per bile component, and the resulting mean and standard deviation, were calculated.
Results
The concentrations of gallbladder components in healthy subjects were: NHCBA: 93 ± 66 mM, OLC: 154 ± 124 mM, CCPL: 42 ± 17 mM, TCBA: 48 ± 35 mM, GCBA: 67 ± 32 mM, ML: 740 ± 391 mM, BALC1.0: 175 ± 92 mM, BALC0.9: 260 ± 138 mM, and TBAC: 153 ± 90 mM. Mean concentrations of all bile components were found to be lower in patients.
Data Conclusion
This work provides a protocol for designing future MRS investigations of the bile system in vivo.
Evidence Level
2
Technical Efficacy Stage
1
Previous in vivo proton MR spectroscopy (MRS) studies have demonstrated the possibility of quantifying amide groups of conjugated bile acids (NHCBA), olefinic lipids and cholesterol (OLC), ...choline-containing phospholipids (CCPLs), taurine and glycine conjugated bile acids (TCBA, GCBA), methylene group of lipids (ML), and methyl groups of bile acids, lipids, and cholesterol (BALC1.0, BALC0.9, and TBAC) in the gallbladder, which may be useful for the study of cholestatic diseases and cholangiopathies. However, these studies were performed at 1.5T and 3T, and higher magnetic fields may offer improved spectral resolution and signal intensity.
To develop a method for gallbladder MRS at 7T.
Retrospective, technical development.
Ten healthy subjects (five males and five females), two patients with primary biliary cholangitis (PBC) (one male and one female), and one patient with primary sclerosing cholangitis (PSC) (female).
Free-breathing single-voxel MRS with a modified stimulated echo acquisition mode (STEAM) sequence at 7T.
Postprocessing was based on the T
relaxation of water in the gallbladder and in the liver. Concentrations of biliary components were calculated using water signal. All data were corrected for T
relaxation times measured in healthy subjects.
The range of T
relaxation time and concentration per bile component, and the resulting mean and standard deviation, were calculated.
The concentrations of gallbladder components in healthy subjects were: NHCBA: 93 ± 66 mM, OLC: 154 ± 124 mM, CCPL: 42 ± 17 mM, TCBA: 48 ± 35 mM, GCBA: 67 ± 32 mM, ML: 740 ± 391 mM, BALC1.0: 175 ± 92 mM, BALC0.9: 260 ± 138 mM, and TBAC: 153 ± 90 mM. Mean concentrations of all bile components were found to be lower in patients.
This work provides a protocol for designing future MRS investigations of the bile system in vivo.
2 TECHNICAL EFFICACY STAGE: 1.
Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to intramyocellular ...lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (
H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control.
Acetylcarnitine and intramyocellular lipid concentrations were measured in 35 individuals stratified into three groups according to glucose tolerance and/or manifestation of type 2 diabetes mellitus. All MRS measurements were performed on a 3-T MR system.
The differences in patient phenotype were mirrored by increased intramyocellular lipids in the tibialis anterior and decreased acetylcarnitine concentrations in the soleus muscle of type 2 diabetes patients when compared with normal glucose-tolerant individuals. Results suggest that intramyocellular lipids mirror whole-body glucose tolerance better in the tibialis anterior muscle, whereas acetylcarnitine is a better discriminator in the soleus muscle.
This muscle-specific behavior of metabolites could represent different fiber compositions in the examined muscles and should be considered when planning future metabolic studies.
Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic diseases. Our knowledge of ...mechanisms responsible for this decline is limited. Glycerophosphocholine phosphodiesterase 1 (Gpcpd1) is a highly abundant muscle enzyme that hydrolyzes glycerophosphocholine (GPC). The physiological functions of Gpcpd1 remain largely unknown. Here we show, in mice, that the Gpcpd1-GPC metabolic pathway is perturbed in aged muscles. Further, muscle-specific, but not liver- or fat-specific, inactivation of Gpcpd1 resulted in severely impaired glucose metabolism. Western-type diets markedly worsened this condition. Mechanistically, Gpcpd1 muscle deficiency resulted in accumulation of GPC, causing an 'aged-like' transcriptomic signature and impaired insulin signaling in young Gpcpd1-deficient muscles. Finally, we report that the muscle GPC levels are markedly altered in both aged humans and patients with type 2 diabetes, displaying a high positive correlation between GPC levels and chronological age. Our findings reveal that the muscle GPCPD1-GPC metabolic pathway has an important role in the regulation of glucose homeostasis and that it is impaired during aging, which may contribute to glucose intolerance in aging.
Objective
Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to ...intramyocellular lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (1H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control.
Methods
Acetylcarnitine and intramyocellular lipid concentrations were measured in 35 individuals stratified into three groups according to glucose tolerance and/or manifestation of type 2 diabetes mellitus. All MRS measurements were performed on a 3‐T MR system.
Results
The differences in patient phenotype were mirrored by increased intramyocellular lipids in the tibialis anterior and decreased acetylcarnitine concentrations in the soleus muscle of type 2 diabetes patients when compared with normal glucose‐tolerant individuals. Results suggest that intramyocellular lipids mirror whole‐body glucose tolerance better in the tibialis anterior muscle, whereas acetylcarnitine is a better discriminator in the soleus muscle.
Conclusions
This muscle‐specific behavior of metabolites could represent different fiber compositions in the examined muscles and should be considered when planning future metabolic studies.
Background
Daily nutrition plays an important role in supporting training adaptions and endurance performance. The objective of this 10-week study was to investigate the consequences of varying ...carbohydrate consumption and the glycaemic index (GI) together with an endurance training regimen on substrate oxidation, muscle energy storage and endurance performance under free-living conditions. Sixty-five moderately trained healthy men (29 ± 4 years; VO
2
peak 55 ± 8 mL min
−1
kg
−1
) were randomized to one of three different nutritional regimes (LOW-GI: 50–60% CHO with ≥ 65% of these CHO with GI < 50 per day, n = 24; HIGH-GI: 50–60% CHO with ≥ 65% CHO with GI > 70 per day, n = 20; LCHF: ≤ 50 g CHO daily, n = 21). Metabolic alterations and performance were assessed at baseline (T0) and after 10 weeks (T10) during a graded exercise treadmill test. Additionally, a 5 km time trial on a 400-m outdoor track was performed and muscle glycogen was measured by magnet resonance spectroscopy.
Results
Total fat oxidation expressed as area under the curve (AUC) during the graded exercise test increased in LCHF (1.3 ± 2.4 g min
−1
× km h
−1
,
p
< 0.001), remained unchanged in LOW-GI (
p
> 0.05) and decreased in HIGH-GI (− 1.7 ± 1.5 g min
−1
× km h
−1
,
p
< 0.001). After the intervention, LOW-GI (− 0.4 ± 0.5 mmol L
−1
× km h
−1
,
p
< 0.001) and LCHF (− 0.8 ± 0.7 mmol L
−1
× km h
−1
,
p
< 0.001) showed significantly lower AUC of blood lactate concentrations. Peak running speed increased in LOW-GI (T0: 4.3 ± 0.4 vs. T10: 4.5 ± 0.3 m s
−1
,
p
< 0.001) and HIGH-GI (T0: 4.4 ± 0.5 vs. T10: 4.6 ± 0.4 m s
−1
), while no improvement was observed in LCHF. Yet, time trial performance improved significantly in all groups. Muscle glycogen content increased for participants in HIGH-GI (T0: 97.3 ± 18.5 vs. T10: 144.5 ± 39.8 mmol L wet-tissue
−1
,
p
= 0.027) and remained unchanged in the LOW-GI and the LCHF group. At the last examination, muscle glycogen concentration was significantly higher in LOW-GI compared to LCHF (
p
= 0.014).
Conclusion
Changes in fat oxidation were only present in LCHF, however, lower lactate concentrations in LOW-GI resulted in changes indicating an improved substrate metabolism. Compared to a LCHF diet, changes in peak running speed, and muscle glycogen stores were superior in LOW- and HIGH-GI diets. The low GI diet seems to have an influence on substrate metabolism without compromising performance at higher intensities, suggesting that a high-carbohydrate diet with a low GI is a viable alternative to a LCHF or a high GI diet.
Trial registration
: Clinical Trials, NCT05241730.
https://clinicaltrials.gov/study/NCT05241730
. Registered 25 January 2021.
Key Points
While only the LCHF diet showed an improvement in fat oxidation and the HIGH-GI group increased peak running speed and showed a trend towards an improvement in time to exhaustion, the LOW-GI group appears to combine both effects on substrate metabolism and performance.
Administered under free-living conditions, energy intake changed in LOW-GI diet, possible due to higher intake of fibre, stable insulin levels and associated higher feeling of satiety. Energy intake in HIGH-GI showed no changes and in LCHF a trend towards a reduced intake was observed.
While changes in body weight and composition were more pronounced in LOW-GI and LCHF group, muscle energy storage showed beneficial improvements in endurance runners on a high glycaemic index diet. With the muscle glycogen content being significantly lower in LCHF compared to LOW-GI group, it can be assumed that this might be a limiting factor in maximum values for the graded exercise test.
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