| 1. |
- Flockhart, Mikael, et al.
(författare)
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Glucosinolate-rich broccoli sprouts protect against oxidative stress and improve adaptations to intense exercise training.
- 2023
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Ingår i: Redox Biology. - : Elsevier. - 2213-2317. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.
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| 2. |
- Apró, William, 1980-, et al.
(författare)
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Endurance Exercise Does Not Impair mTOR Signalling After Resistance Exercise : D-58 Thematic Poster - Skeletal Muscle Cell Signaling: JUNE 2, 2011 3:15 PM - 5:15 PM: ROOM: 304
- 2011
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Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 43:5, s. 52-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Resistance exercise is known to stimulate muscle hypertrophy and this effect is mainly mediated by the mammalian target of rapamycin (mTOR) pathway. In contrast, endurance exercise results in a divergent phenotypic response which to a large extent is mediated by adenosine monophosphate-activated protein kinase (AMPK). Research indicates that molecular interference may exist, possibly through an inhibitory effect on mTOR signalling by AMPK, when these two modes of exercise are combined. PURPOSE: To investigate the impact of subsequent endurance exercise on resistance exercise induced mTOR signalling. METHODS: In a randomized and cross-over fashion, ten male subjects performed either heavy resistance exercise (R) or heavy resistance exercise followed by endurance exercise (RE) on two separate occasions. The R protocol consisted of thirteen sets of leg press exercise with 3 minutes of recovery allowed between each set. In the RE session, resistance exercise was followed by 15 minutes recovery after which 30 min of cycling was initiated at an intensity equal to 70 % of the subjects' maximal oxygen consumption. Muscle biopsies were collected before, 1 and 3 hours after resistance exercise in both trials. Samples were analyzed for several signalling proteins in the mTOR pathway using western blot technique. RESULTS: Phosphorylation of mTOR increased approx. twofold at 1 h post resistance exercise and remained elevated at the 3 h time point (p< 0.01) with no difference between the two trials. Phosphorylation of p70S6k, a downstream target of mTOR, was increased about 6-and18-fold at 1 h and 3 h post resistance exercise (p< 0.01). There was no difference in p70S6k phosphorylation at any time point between the two trials. Phosphorylation of the eukaryotic elongation factor eEF2 was decreased 3- to 4-fold at both time points post resistance exercise (p< 0.01) with no difference between trials. Phosphorylation of AMPK was unchanged at the 1 h time point but decreased approximately 30 % from pre-exercise values in both trials at 3 h post resistance exercise (p< 0.01). CONCLUSIONS: The signalling response following heavy resistance exercise is not blunted by subsequent endurance exercise. Supported by the Swedish National Centre for Research in Sports.
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| 3. |
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| 4. |
- Blackwood, Sarah J, et al.
(författare)
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Elevated heart rate and decreased muscle endothelial nitric oxide synthase in early development of insulin resistance.
- 2024
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555.
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations. Biopsies were obtained from the thigh muscle, followed by an intravenous glucose tolerance test. Indices of insulin action were calculated and cardiovascular measurements, analyses of blood and muscle were performed. Whole-body insulin sensitivity (SIgalvin) was positively related to expression of type I muscle fibers (r=0.49; P<0.001) and negatively related to resting heart rate (HR, r=-0.39; P<0.001), which was also negatively related to expression of type I muscle fibers (r=-0.41; P<0.001). Muscle protein expression of endothelial nitric oxide synthase (eNOS), whose activation results in vasodilation, was measured in two subsets of subjects expressing a high percentage of type I fibers (59±6%; HR = 57±9 beats/min; SIgalvin = 1.8±0.7 units) or low percentage of type I fibers (30±6%; HR = 71±11; SIgalvin = 0.8±0.3 units; P<0.001 for all variables vs. first group). eNOS expression was: 1. higher in subjects with high type I expression; 2. almost two-fold higher in pools of type I vs. II fibers; 3. only detected in capillaries surrounding muscle fibers; and 4. linearly associated with SIgalvin. These data demonstrate that an altered function of the autonomic nervous system and a compromised capacity for vasodilation in the microvasculature occur early in the development of IR.
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| 5. |
- Blackwood, Sarah J, et al.
(författare)
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Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion.
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:7, s. e2729-e2737
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Muscle fiber composition is associated with peripheral insulin action.OBJECTIVE: We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia.METHODS: Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group I (n=11), area occupied by type I muscle fibers = 61.0 ± 11.8%; group II (n=8), type I area = 36.0 ± 4.9% (P<0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity and secretion were determined.RESULTS: Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group II vs group I (P=0.019). First phase insulin release (area under the insulin curve during 10 min after glucose infusion) was increased by almost 4-fold in group II vs I (P=0.01). Whole-body insulin sensitivity was correlated with % area occupied by type I fibers (r=0.54; P=0.018) and capillary density in muscle (r=0.61; P=0.005), but not with mitochondrial respiration. Insulin release was strongly related to % area occupied by type II fibers (r=0.93; P<0.001).CONCLUSIONS: Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose stimulated insulin secretion prior to onset of clinical manifestations.
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| 6. |
- Blackwood, Sarah J, et al.
(författare)
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Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.
- 2023
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 324:5, s. E390-E401
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Tidskriftsartikel (refereegranskat)abstract
- There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: 1, area occupied by type I fibers = 61.0 ± 11.8%; 2, type I area = 36.0 ± 4.9% (P<0.001). Muscle biopsies and intravenous glucose tolerance tests were performed after an overnight fast and after starvation. Biopsies were analyzed for muscle fiber composition and mitochondrial respiration. Indices of glucose tolerance and insulin sensitivity were determined. Glucose tolerance was similar in both groups after an overnight fast and deteriorated to a similar degree in both groups after starvation. In contrast, whole-body insulin sensitivity decreased markedly after starvation in group 1 (P<0.01), whereas the decrease in group 2 was substantially smaller (P=0.06). Non-esterified fatty acids and β-hydroxybutyrate levels in plasma after an overnight fast were similar between groups and increased markedly and comparably in both groups after starvation, demonstrating similar degrees of lipid load. The capacity of permeabilized muscle fibers to oxidize lipids was significantly higher in group 1 vs. 2, whereas there was no significant difference in pyruvate oxidation between groups. The data demonstrate that loss of whole-body insulin sensitivity after short-term starvation is a function of muscle fiber composition and is associated with an elevated rather than a diminished capacity of muscle to oxidize lipids.
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| 7. |
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| 8. |
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| 9. |
- Edman, Sebastian, et al.
(författare)
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mTORC1 Signaling in Individual Human Muscle Fibers Following Resistance Exercise in Combination With Intake of Essential Amino Acids
- 2019
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Human muscles contain a mixture of type I and type II fibers with different contractile and metabolic properties. Little is presently known about the effect of anabolic stimuli, in particular nutrition, on the molecular responses of these different fiber types. Here, we examine the effect of resistance exercise in combination with intake of essential amino acids (EAA) on mTORC1 signaling in individual type I and type II human muscle fibers. Five strength-trained men performed two sessions of heavy leg press exercise. During exercise and recovery, the subjects ingested an aqueous solution of EAA (290 mg/kg) or flavored water (placebo). Muscle biopsies were taken from the vastus lateralis before and 90 min after exercise. The biopsies were freeze-dried and single fibers dissected out and weighed (range 0.95-8.1 mu g). The fibers were homogenized individually and identified as type I or II by incubation with antibodies against the different isoforms of myosin. They were also analyzed for both the levels of protein as well as phosphorylation of proteins in the mTORC1 pathway using Western blotting. The levels of the S6K1 and eEF2 proteins were similar to 50% higher in type II than in type I fibers (P < 0.05), but no difference was found between fiber types with respect to the level of mTOR protein. Resistance exercise led to non-significant increases (2-3-fold) in mTOR and S6K1 phosphorylation as well as a 50% decrease (P < 0.05) in eEF2 phosphorylation in both fiber types. Intake of EAA caused a 2 and 6-fold higher (P < 0.05) elevation of mTOR and S6K1 phosphorylation, respectively, in both type I and type II fibers compared to placebo, with no effect on phosphorylation of eEF2. In conclusion, protein levels of S6K1 and eEF2 were significantly higher in type II than type I fibers suggesting higher capacity of the mTOR pathway in type II fibers. Ingestion of EAA enhanced the effect of resistance exercise on phosphorylation of mTOR and S6K1 in both fiber types, but with considerable variation between single fibers of both types.
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| 10. |
- Edman, Sebastian, et al.
(författare)
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Need for speed : Human fast-twitch mitochondria favor power over efficiency
- 2024
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Ingår i: Molecular Metabolism. - : Elsevier. - 2212-8778. ; 79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Human skeletal muscle consists of a mixture of slow- and fast-twitch fibers with distinct capacities for contraction mechanics, fermentation, and oxidative phosphorylation. While the divergence in mitochondrial volume favoring slow-twitch fibers is well established, data on the fiber type-specific intrinsic mitochondrial function and morphology are highly limited with existing data mainly being generated in animal models. This highlights the need for more human data on the topic.Methods: Here, we utilized THRIFTY, a rapid fiber type identification protocol to detect, sort, and pool fast- and slow-twitch fibers within 6 h of muscle biopsy sampling. Respiration of permeabilized fast- and slow-twitch fiber pools was then analyzed with high-resolution respirometry. Using standardized western blot procedures, muscle fiber pools were subsequently analyzed for control proteins and key proteins related to respiratory capacity.Results: Maximal complex I+II respiration was 25% higher in human slow-twitch fibers compared to fast-twitch fibers. However, per mitochondrial volume, the respiratory rate of mitochondria in fast-twitch fibers was approximately 50% higher for complex I+II, which was primarily mediated through elevated complex II respiration. Furthermore, the abundance of complex II protein and proteins regulating cristae structure were disproportionally elevated in mitochondria of the fast-twitch fibers. The difference in intrinsic respiratory rate was not reflected in fatty acid–or complex I respiration.Conclusion: Mitochondria of human fast-twitch muscle fibers compensate for their lack of volume by substantially elevating intrinsic respiratory rate through increased reliance on complex II.
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| 11. |
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| 12. |
- Edman, Sebastian, et al.
(författare)
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Pro-Brain-Derived Neurotrophic Factor (BDNF), but Not Mature BDNF, Is Expressed in Human Skeletal Muscle : Implications for Exercise-Induced Neuroplasticity.
- 2024
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Ingår i: Function. - : Oxford University Press. - 2633-8823. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Exercise promotes brain plasticity partly by stimulating increases in mature brain-derived neurotrophic factor (mBDNF), but the role of the pro-BDNF isoform in the regulation of BDNF metabolism in humans is unknown. We quantified the expression of pro-BDNF and mBDNF in human skeletal muscle and plasma at rest, after acute exercise (+/- lactate infusion), and after fasting. Pro-BDNF and mBDNF were analyzed with immunoblotting, enzyme-linked immunosorbent assay, immunohistochemistry, and quantitative polymerase chain reaction. Pro-BDNF was consistently and clearly detected in skeletal muscle (40-250 pg mg-1 dry muscle), whereas mBDNF was not. All methods showed a 4-fold greater pro-BDNF expression in type I muscle fibers compared to type II fibers. Exercise resulted in elevated plasma levels of mBDNF (55%) and pro-BDNF (20%), as well as muscle levels of pro-BDNF (∼10%, all P < 0.05). Lactate infusion during exercise induced a significantly greater increase in plasma mBDNF (115%, P < 0.05) compared to control (saline infusion), with no effect on pro-BDNF levels in plasma or muscle. A 3-day fast resulted in a small increase in plasma pro-BDNF (∼10%, P < 0.05), with no effect on mBDNF. Pro-BDNF is highly expressed in human skeletal muscle, particularly in type I fibers, and is increased after exercise. While exercising with higher lactate augmented levels of plasma mBDNF, exercise-mediated increases in circulating mBDNF likely derive partly from release and cleavage of pro-BDNF from skeletal muscle, and partly from neural and other tissues. These findings have implications for preclinical and clinical work related to a wide range of neurological disorders such as Alzheimer's, clinical depression, and amyotrophic lateral sclerosis.
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| 13. |
- Edman, Sebastian, 1990-
(författare)
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Skeletal muscle fiber types in man : With special reference to anabolic signaling and mitochondrial bioenergetics
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human skeletal muscle consists of a mixture of slow-twitch (type I) and fast-twitch (type II) fibers. The type I fibers are endurance-oriented, with a metabolic system and infrastructure that supports aerobic metabolism. This entails a well-developed capillary grid and a mitochondrial network proportioned to the number of contractile units within the fiber. These fibers generally have slower and less forceful contraction mechanics and more limited muscle growth as a resource-efficient metabolic energy system is prioritized over increasing the number of contractile units. By contrast, type II fibers prioritize contractile capabilities and force generation at the cost of resource efficiency. These fibers have a substantially lower mitochondrial volume but prioritize structures and organelles that benefit muscle contraction instead. It is well known that resistance exercise combined with dietary protein intake stimulates the growth of contractile proteins leading to an increased muscle mass over time. Muscle mass accumulation is primarily driven by the amplification of muscle protein synthesis, which in turn is largely governed by the mTORC1 signaling pathway within the muscle cell. Little is known about how mTORC1 signaling regulates growth in the different fiber types. Furthermore, it is unknown whether blunted anabolic signaling in type II fibers of the elderly may explain why losses of muscle mass occur primarily in these fibers with advancing age.Endurance exercise, on the other hand, primarily stimulates a prioritization to synthesize new mitochondria to support the high demand for sustainable aerobic energy output. However, it remains to be determined if mitochondria created within type I and type II fibers are equal, or whether they have adapted to their respective milieu in any way. Therefore, the aim of the current thesis was to investigate how the mTORC1 pathway in type I and type II fibers responds to resistance exercise and nutritional stimuli in the form of essential amino acids (EAA), and to determine if this response is influenced by age. Fiber type-specific mitochondrial populations, including their respiratory capacity, were also investigated. To facilitate these investigations, a new and improved method for muscle fiber type identification was developed.In paper I, the phosphorylation of mTORC1 in response to resistance exercise and EAA intake was examined in 684 individual muscle fibers. Unsurprisingly, a significant increase in mTORC1 signaling was seen following the combination of resistance exercise and EAA intake, whereas the rise following resistance exercise alone was more modest. However, no evidence of a discrete response in the different fiber types was found. In paper II, a new method was developed to facilitate the work surrounding fiber type-specific muscle physiology by limiting the extreme time requirements of fiber type identification of large sample sets of muscle fibers. The novel method, which was named THRIFTY, allows an experienced technician to classify over 800 fibers in under 11h.Paper III utilizes the high throughput of the THRIFTY method described in paper II to create the most extensive study to date on individually dissected muscle fibers with 27 602 included fibers. Here, the aim was to investigate whether the fiber type-specific muscle atrophy of the type II fibers in aging could be explained by an onset of anabolic resistance in these fibers. For this investigation, ten young and ten elderly men were recruited to perform a unilateral resistance exercise session followed by ingestion of EAA. This paper showed a slightly elevated mTORC1 signaling response in type I fibers. However, there were no signs of blunted mTORC1 signaling in the elderly. In paper IV, the high speed of the THRIFTY method was utilized to analyze the mitochondrial respiratory function of permeabilized type I and type II muscle fibers. In addition, the intrinsic protein expression of mitochondria in the type I and type II muscle fibers was analyzed. As expected, a higher volume of mitochondria and a greater respiratory rate in the type I fibers were found. However, on a per mitochondria basis, a higher maximal respiratory rate was observed in type II fibers together with increased levels of proteins in the electron transport chain. Likewise, proteins regulating mitochondrial fission and fusion were more highly expressed in the type II fiber mitochondria, which may be a compensatory mechanism for the low volume. In conclusion, both fiber types show robust increases in mTORC1 signaling in response to exercise and EAA ingestion. The results indicate that the response is slightly stronger in the type I fibers, which is contrary to what was predicted. Moreover, the highly specific type II fiber atrophy seen with aging cannot be explained by a blunted anabolic response in these fibers. Surprisingly, the mitochondria of type II fibers possess a higher respiratory capacity. However, this discrepancy is concealed by the vast difference in mitochondrial volume favoring type I fibers, ultimately leading to an overall greater respiratory rate in the type I fibers.
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| 14. |
- Edman, Sebastian, et al.
(författare)
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THRIFTY - A High-throughput Single Muscle Fiber Typing Method Based on Immunofluorescence Detection
- 2023
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Ingår i: Bio-protocol. - : Bio-protocol. - 2331-8325. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle consists of a mixture of fiber types with different functional and metabolic characteristics. The relative composition of these muscle fiber types has implications for muscle performance, whole-body metabolism, and health. However, analyses of muscle samples in a fiber type-dependent manner are very time consuming. Therefore, these are often neglected in favor of more time-efficient analyses on mixed muscle samples. Methods such as western blot and myosin heavy chain separation by SDS-PAGE have previously been utilized to fiber type-isolated muscle fibers. More recently, the introduction of the dot blot method significantly increased the speed of fiber typing. However, despite recent advancements, none of the current methodologies are feasible for large-scale investigations because of their time requirements. Here, we present the protocol for a new method, which we have named THRIFTY (high-THRoughput Immunofluorescence Fiber TYping), that enables rapid fiber type identification using antibodies towards the different myosin heavy chain (MyHC) isoforms of fast and slow twitch muscle fibers. First, a short segment (<1 mm) is cut off from isolated muscle fibers and mounted on a customized gridded microscope slide holding up to 200 fiber segments. Second, the fiber segments attached to the microscope slide are stained with MyHC-specific antibodies and then visualized using a fluorescence microscope. Lastly, the remaining pieces of the fibers can either be collected individually or pooled together with fibers of the same type for subsequent analyses. The THRIFTY protocol is approximately three times as fast as the dot blot method, which enables not only time-sensitive assays to be performed but also increases the feasibility to conduct large-scale investigations into fiber type specific physiology.
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| 15. |
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| 16. |
- Flockhart, Mikael, et al.
(författare)
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Dose-response relationship between exercise load and mitochondrial function
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Dose-response relationship between exercise load and mitochondrial functionFlockhart M, Nilsson L, Bergman K, Apro W, Ekblom B, Larsen FJA dose-dependent relationship exists between exercise load and muscular adaptation. Mitochondria adapt to the increased ATP-demand by alterations in mass and/or quality. How mitochondrial mass and quality changes as a function of exercise load is not well investigated and we have previously found mitochondrial dysfunction after short-term intensive exercise. We therefore aimed to study mitochondrial function by altering exercise load during a three week interval training regimen to understand the dose-response relationship between exercise load and mitochondrial function. We took four muscle biopsies throughout the study, and as expected, mitochondrial function was positively affected during the first two weeks. After the third week, a dramatic mitochondrial dysfunction was evident as mitochondrial intrinsic respiration was reduced by 26% despite a 32% increase in mitochondrial yield. We hereby present evidence of a striking exercise-induced reduction in mitochondrial function after a period of very intense interval training.
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| 17. |
- Flockhart, Mikael, et al.
(författare)
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Excessive exercise training causes mitochondrial functional impairment and decreases glucose tolerance in healthy volunteers.
- 2021
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Ingår i: Cell Metabolism. - : Cell Press. - 1550-4131 .- 1932-7420. ; 33:5, s. 957-970
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Tidskriftsartikel (refereegranskat)abstract
- Exercise training positively affects metabolic health through increased mitochondrial oxidative capacity and improved glucose regulation and is the first line of treatment in several metabolic diseases. However, the upper limit of the amount of exercise associated with beneficial therapeutic effects has not been clearly identified. Here, we used a training model with a progressively increasing exercise load during an intervention over 4 weeks. We closely followed changes in glucose tolerance, mitochondrial function and dynamics, physical exercise capacity, and whole-body metabolism. Following the week with the highest exercise load, we found a striking reduction in intrinsic mitochondrial function that coincided with a disturbance in glucose tolerance and insulin secretion. We also assessed continuous blood glucose profiles in world-class endurance athletes and found that they had impaired glucose control compared with a matched control group.
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| 18. |
- Flockhart, Mikael, et al.
(författare)
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Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.
- 2023
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 238:4
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3. determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses to the exercise paradigms.METHODS: Nine endurance athletes (END) and eight healthy nonendurance-trained controls (CON) were studied. Oral glucose tolerance tests (OGTT) and mitochondrial function were assessed on three occasions: in the morning, 14 h after an overnight fast without prior exercise (RE), as well as after 3 h of prolonged continuous exercise at 65% of VO2 max (PE) or 5 × 4 min at ~95% of VO2 max (HIIT) on a cycle ergometer.RESULTS: Glucose tolerance was markedly reduced in END after PE compared with RE. END also exhibited elevated fasting serum FFA and ketones levels, reduced insulin sensitivity and glucose oxidation, and increased fat oxidation during the OGTT. CON showed insignificant changes in glucose tolerance and the aforementioned measurements compared with RE. HIIT did not alter glucose tolerance in either group. Neither PE nor HIIT affected mitochondrial function in either group. END also exhibited increased activity of 3-hydroxyacyl-CoA dehydrogenase activity in muscle extracts vs. CON.CONCLUSION: Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.
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| 19. |
- Flockhart, Mikael, et al.
(författare)
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THREE HOURS OF MODERATE INTENSITY EXERCISE TRAINING REDUCES GLUCOSE TOLERANCE IN ENDURANCE TRAINED ATHLETES
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUNDIt is well accepted that exercise training improves glucose uptake and insulin sensitivity, and that endurance trained athletes in general show a high capacity for these parameters and excellent metabolic control. However, some studies fail to observe positive effects on glucose regulation in healthy, trained subjects the day after exercise. These, often unexpected, results have been postulated to be caused by excessive training loads, muscle damage, energy deficit, differences in glucose uptake in the exercised and non-exercised musculature and a metabolic interaction through increased fatty acid metabolism which suppresses glucose oxidation and uptake. The mode or volume of exercise that can lead to glucose intolerance in trained athletes as well as mechanistic insights and its relevance for health and performance are, however, not fully understood.AIMWe studied the metabolic response to a glucose load the day after a session of high intensity interval training (HIIT) or three hours of continuous exercise (3h) in endurance trained athletes and compared the results with measurements during rest.METHODNine endurance trained athletes (5 females, 4 males) underwent oral glucose tolerance tests (OGTT) after rest and ~14 hours after exercise on a cycle ergometer (HIIT 5x4 minutes at ~95% of VO2max or 3h at 65% of VO2max). Venous blood was sampled at 15-minute intervals for 120 minutes and concentrations of glucose, insulin, free fatty acids (FFA) and ketones (β-hydroxybutyrate) were measured. Statistical analysis was performed using a RM one-way ANOVA with the Giesser-Greenhouse correction and Dunnett’s test was used to compare the exercise conditions to the resting condition.RESULTSThe area under the curve (AUC) during the OGTT increased greatly after 3h (668±124 mM · min) (p<0.01) compared to rest (532±89) but was found to be unchanged after HIIT (541±96). Resting values of FFA and ketones were increased after 3h (p<0.01 and p<0.05, respectively) but not after HIIT. Insulin was found to be unaltered during all conditions.CONCLUSIONS AND RELEVANCEHere, we show manifestation of glucose intolerance in endurance trained athletes together with concomitant increases in plasma concentrations of FFA and ketones the day after a session of prolonged exercise training but not after HIIT. This could be a protective response for securing glucose delivery to the brain and therefore have a positive effect on endurance. It also has the potential to reduce the recovery of glycogen depots, glucose uptake during exercise and performance at higher work rates.
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| 20. |
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| 21. |
- Hammarström, Daniel, et al.
(författare)
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Benefits of higher resistance-training volume are related to ribosome biogenesis.
- 2020
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Ingår i: Journal of Physiology. - : John Wiley & Sons. - 0022-3751 .- 1469-7793. ; 598:3, s. 543-565
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Tidskriftsartikel (refereegranskat)abstract
- KEY POINTS: For individuals showing suboptimal adaptations to resistance training, manipulation of training volume is a potential measure to facilitate responses. This remains unexplored. Here, 34 untrained individuals performed contralateral resistance training with moderate and low volume for 12 weeks. Moderate volume led to larger increases in muscle cross-sectional area, strength and type II fibre-type transitions. These changes coincided with greater activation of signalling pathways controlling muscle growth and greater induction of ribosome synthesis. Thirteen and sixteen participants, respectively, displayed clear benefits of moderate-volume training on muscle hypertrophy and strength. This coincided with greater total RNA accumulation in the early-phase of the training period, suggesting that ribosomal biogenesis regulates the dose-response relationship between training volume and muscle hypertrophy. These results demonstrate that there is a dose-dependent relationship between training volume and outcomes. On the individual level, benefits of higher training volume were associated with increased ribosomal biogenesis.ABSTRACT: Resistance-exercise volume is a determinant of training outcomes. However not all individuals respond in a dose-dependent fashion. In this study, 34 healthy individuals (males n = 16, 23.6 (4.1) years; females n = 18, 22.0 (1.3)) performed moderate- (3 sets per exercise, MOD) and low-volume (1 set, LOW) resistance training in a contralateral fashion for 12 weeks (2-3 sessions × week-1 ). Muscle cross-sectional area (CSA) and strength were assessed at weeks 0 and 12, along with biopsy sampling (m. Vastus lateralis). Muscle biopsies were also sampled before and one hour after the fifth session (Week 2). MOD resulted in larger increases in muscle CSA (5.2 (3.8)% versus 3.7 (3.7)%, P < 0.001) and strength (3.4-7.7% difference, all P < 0.05. This coincided with greater reductions in type IIX fibres from week 0 to 12 (MOD, -4.6; LOW -3.2%-point), greater phosphorylation of S6-kinase 1 (p85 S6K1Thr412 , 19%; p70 S6K1Thr389 , 58%) and ribosomal protein S6Ser235/236 (37%), greater rested-state total RNA (8.8%) and greater exercise-induced c-Myc mRNA expression (25%; Week 2, all P < 0.05). Thirteen and sixteen participants, respectively, displayed clear benefits in response to MOD on muscle hypertrophy and strength. Benefits were associated with greater accumulation of total RNA at Week 2 in the MOD leg, with every 1% difference increasing the odds of MOD benefit by 7.0% (P = 0.005) and 9.8% (P = 0.002). In conclusion, MOD led to greater functional and biological adaptations than LOW. Associations between dose-dependent total RNA accumulation and increases in muscle mass and strength points to ribosome biogenesis as a determinant of dose-dependent training responses. This article is protected by copyright. All rights reserved.
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| 22. |
- Horwath, Oscar, 1991-, et al.
(författare)
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Acute hypoxia attenuates resistance exercise-induced ribosome signaling but does not impact satellite cell pool expansion in human skeletal muscle.
- 2023
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Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 37:3
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Tidskriftsartikel (refereegranskat)abstract
- Cumulative evidence supports the hypothesis that hypoxia acts as a regulator of muscle mass. However, the underlying molecular mechanisms remain incompletely understood, particularly in human muscle. Here we examined the effect of hypoxia on signaling pathways related to ribosome biogenesis and myogenic activity following an acute bout of resistance exercise. We also investigated whether hypoxia influenced the satellite cell response to resistance exercise. Employing a randomized, crossover design, eight men performed resistance exercise in normoxia (FiO2 21%) or normobaric hypoxia (FiO2 12%). Muscle biopsies were collected in a time-course manner (before, 0, 90, 180 min and 24 h after exercise) and were analyzed with respect to cell signaling, gene expression and satellite cell content using immunoblotting, RT-qPCR and immunofluorescence, respectively. In normoxia, resistance exercise increased the phosphorylation of RPS6, TIF-1A and UBF above resting levels. Hypoxia reduced the phosphorylation of these targets by ~37%, ~43% and ~ 67% throughout the recovery period, respectively (p < .05 vs. normoxia). Resistance exercise also increased 45 S pre-rRNA expression and mRNA expression of c-Myc, Pol I and TAF-1A above resting levels, but no differences were observed between conditions. Similarly, resistance exercise increased mRNA expression of myogenic regulatory factors throughout the recovery period and Pax7+ cells were elevated 24 h following exercise in mixed and type II muscle fibers, with no differences observed between normoxia and hypoxia. In conclusion, acute hypoxia attenuates ribosome signaling, but does not impact satellite cell pool expansion and myogenic gene expression following a bout of resistance exercise in human skeletal muscle.
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| 23. |
- Horwath, Oscar, 1991-, et al.
(författare)
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Fiber type-specific hypertrophy and increased capillarization in skeletal muscle following testosterone administration of young women.
- 2020
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 128:5, s. 1240-1250
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Tidskriftsartikel (refereegranskat)abstract
- It is well established that testosterone administration induces muscle fiber hypertrophy and myonuclear addition in men, however, it remains to be determined whether similar morphological adaptations can be achieved in women. The aim of the present study was therefore to investigate whether exogenously administered testosterone alters muscle fiber morphology in skeletal muscle of young healthy, physically active women. Thirty-five young (20-35 years), recreationally trained women were randomly assigned to either 10-week testosterone administration (10 mg daily) or placebo. Before and after the intervention, hormone concentrations and body composition were assessed, and muscle biopsies were obtained from the vastus lateralis. Fiber type composition, fiber size, satellite cell- and myonuclei content, as well as muscle capillarization were assessed in a fiber type-specific manner using immunohistochemistry. Following the intervention, testosterone administration elevated serum testosterone concentration (5.1-fold increase, P=0.001), and induced significant accretion of total lean mass (+1.9%, P=0.002) and leg lean mass (+2.4%, P=0.001). On the muscle fiber level, testosterone increased mixed fiber cross-sectional area (+8.2%, P=0.001), an effect primarily driven by increases in type II fiber size (9.2%, P=0.006). Whereas myonuclei content remained unchanged, a numerical increase (+30.8%) was found for satellite cells associated with type II fibers in the Testosterone group. In parallel with fiber hypertrophy, testosterone significantly increased capillary contacts (+7.5%, P=0.015) and capillary-to-fiber ratio (+9.2%, P=0.001) in type II muscle fibers. The current study provides novel insight into fiber type-specific adaptations present already after 10 weeks of only moderately elevated testosterone levels in women.
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| 24. |
- Horwath, Oscar, 1991-, et al.
(författare)
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Influence of sex- and fiber type on the satellite cell pool in human skeletal muscle.
- 2021
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 31:2, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- The repair, remodeling and regeneration of myofibers is dependent on satellite cells (SCs), although, the distribution of SCs in different fiber types of human muscle remains inconclusive. There is also a paucity of research comparing muscle fiber characteristics in a sex-specific manner. Therefore, the aim of this study was to investigate fiber type-specific SC content in men and women. Muscle biopsies from vastus lateralis were collected from 64 young (mean age 27 ± 5), moderately trained men (n=34) and women (n=30). SCs were identified by Pax7-staining together with immunofluorescent analyses of fiber type composition, fiber size and myonuclei content. In a mixed population, comparable number of SCs were associated to type I and type II fibers (0.07 ± 0.02 vs 0.07 ± 0.02 SCs per fiber, respectively). However, unlike men, women displayed a fiber type-specific distribution, with SC content being lower in type II than type I fibers (P=0.041). Sex-based differences were found specifically for type II fibers, where women displayed lower SC content compared to men (P<0.001). In addition, positive correlations (r-values between 0.36-0.56) were found between SC content and type I and type II fiber size in men (P=0.03 and P<0.01, respectively), whereas similar relationships could not be detected in women. Sex-based differences were also noted for fiber type composition and fiber size, but not for myonuclei content. We hereby provide evidence for sex-based differences present at the myocellular level, which may have important implications when studying exercise- and training induced myogenic responses in skeletal muscle.
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| 25. |
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| 26. |
- Horwath, Oscar, 1991-, et al.
(författare)
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Molecular Regulators of Muscle Mass and Mitochondrial Remodeling Are Not Influenced by Testosterone Administration in Young Women.
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone (T) administration has previously been shown to improve muscle size and oxidative capacity. However, the molecular mechanisms underlying these adaptations in human skeletal muscle remain to be determined. Here, we examined the effect of moderate-dose T administration on molecular regulators of muscle protein turnover and mitochondrial remodeling in muscle samples collected from young women. Forty-eight healthy, physically active, young women (28 ± 4 years) were assigned in a random double-blind fashion to receive either T (10 mg/day) or placebo for 10-weeks. Muscle biopsies collected before and after the intervention period were divided into sub-cellular fractions and total protein levels of molecular regulators of muscle protein turnover and mitochondrial remodeling were analyzed using Western blotting. T administration had no effect on androgen receptor or 5α-reductase levels, nor on proteins involved in the mTORC1-signaling pathway (mTOR, S6K1, eEF2 and RPS6). Neither did it affect the abundance of proteins associated with proteasomal protein degradation (MAFbx, MuRF-1 and UBR5) and autophagy-lysosomal degradation (AMPK, ULK1 and p62). T administration also had no effect on proteins in the mitochondria enriched fraction regulating mitophagy (Beclin, BNIP3, LC3B-I, LC3B-II and LC3B-II/I ratio) and morphology (Mitofilin), and it did not alter the expression of mitochondrial fission- (FIS1 and DRP1) or fusion factors (OPA1 and MFN2). In summary, these data indicate that improvements in muscle size and oxidative capacity in young women in response to moderate-dose T administration cannot be explained by alterations in total expression of molecular factors known to regulate muscle protein turnover or mitochondrial remodeling.
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| 27. |
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| 28. |
- Horwath, Oscar, 1991-, et al.
(författare)
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THRIFTY : a novel high-throughput method for rapid fibre type identification of isolated skeletal muscle fibres.
- 2022
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Ingår i: Journal of Physiology. - : The physiological society. - 0022-3751 .- 1469-7793. ; 600:20, s. 4421-4438
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Tidskriftsartikel (refereegranskat)abstract
- Fibre type-specific analyses are required for broader understanding of muscle physiology, but such analyses are difficult to conduct due to the extreme time requirements of dissecting and fibre typing individual fibres. Investigations are often confined to a small number of fibres from few participants with low representativeness of the entire fibre population and the participant population. To increase the feasibility of conducting large-scale fibre type-specific studies, a valid and rapid method for high-throughput fibre typing of individually dissected fibres was developed and named THRIFTY (for high-THRoughput Immunofluorescence Fibre TYping). Employing THRIFTY, 400 fibre segments were fixed onto microscope slides with a pre-printed coordinated grid system, probed with antibodies against myosin heavy chain (MyHC)-I and MyHC-II and classified using a fluorescence microscope. The validity and speed of THRIFTY was compared to a previously validated protocol (dot blot) on a fibre-to-fibre basis. Fibre pool purity was evaluated using 'gold standard' SDS-PAGE and silver staining. A modified THRIFTY-protocol using fluorescence western blot equipment was also validated. THRIFTY displayed excellent agreement with the dot blot protocol, κ = 0.955 (95% CI: 0.928, 0.982), P < 0.001. Both the original and modified THRIFTY protocols generated type I and type II fibre pools of absolute purity. Using THRIFTY, 400 fibres were typed just under 11 h, which was approximately 3 times faster than dot blot. THRIFTY is a novel and valid method with high versatility for very rapid fibre typing of individual fibres. THRIFTY can therefore facilitate the generation of large fibre pools for more extensive mechanistic studies into skeletal muscle physiology. KEY POINTS: Skeletal muscle is composed of different fibre types, each with distinct physiological properties. To fully understand how skeletal muscle adapts to external cues such as exercise, nutrition and ageing, fibre type-specific investigations are required. Such investigations are very difficult to conduct due to the extreme time requirements related to classifying individually isolated muscle fibres. To bypass this issue, we have developed a rapid and reliable method named THRIFTY which is cheap as well as versatile and which can easily be implemented in most laboratories. THRIFTY increases the feasibility of conducting larger fibre type-specific studies and enables time-sensitive assays where measurements need to be carried out in close connection with tissue sampling. By using THRIFTY, new insights into fibre type-specific muscle physiology can be gained which may have broad implications in health and disease.
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| 29. |
- Horwath, Oscar, 1991-, et al.
(författare)
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Variablity in vastus lateralis fiber type distribution, fiber size and myonuclear content along and between the legs.
- 2021
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 131:1, s. 158-173
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Tidskriftsartikel (refereegranskat)abstract
- Human skeletal muscle characteristics such as fiber type composition, fiber size and myonuclear content are widely studied in clinical and sports related contexts. Being aware of the methodological and biological variability of the characteristics is a critical aspect in study design and outcome interpretation, but comprehensive data on the variability of morphological features in human skeletal muscle is currently limited. Accordingly, in the present study, m. vastus lateralis biopsies (10 per subject) from young and healthy individuals, collected in a systematic manner, were analyzed for various characteristics using immunohistochemistry (n=7) and SDS-PAGE (n=25). None of the analyzed parameters; fiber type % (FT%), type I and II CSA (fCSA), percentage fiber type area (fCSA%), myosin heavy chain composition (MyHC%), type IIX content, myonuclear content or myonuclear domain varied in a systematic manner longitudinally along the muscle or between the two legs. The average within subject coefficient of variation for FT%, fCSA, fCSA%, and MyHC% ranged between 13-18%, but was only 5% for fiber specific myonuclear content, which reduced the variability for myonuclear domain size to 11-12%. Pure type IIX fibers and type IIX MyHC were randomly distributed and present in <24% of the analyzed samples, with the average content being 0.1 and 1.1%, respectively. In conclusion, leg or longitudinal orientation does not seem to be an important aspect to consider when investigating human vastus lateralis characteristics. However, single muscle biopsies should preferably not be used when studying fiber type and fiber size related aspects given the notable sample to sample variability.
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| 30. |
- Liegnell, Rasmus, et al.
(författare)
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Elevated plasma lactate levels via exogenous lactate infusion do not alter resistance exercise-induced signaling or protein synthesis in human skeletal muscle.
- 2020
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 319, s. E792-E804
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Tidskriftsartikel (refereegranskat)abstract
- Lactate has been implicated as a potential signaling molecule. In myotubes, lactate incubation increases mTORC1- and ERK-signaling and induces hypertrophy, indicating that lactate could be a mediator of muscle adaptations to resistance exercise. However, the potential signaling properties of lactate, at rest or with exercise, have not been explored in human tissue. In a cross-over design study, 8 men and 8 women performed one-legged resistance exercise while receiving venous infusion of saline or sodium lactate. Blood was sampled repeatedly, and muscle biopsies were collected at rest and at 0, 90,180 min and 24 h after exercise. The primary outcomes examined were intracellular signaling, fractional protein synthesis rate (FSR), and blood/muscle levels of lactate and pH. Post-exercise blood lactate concentrations were 130% higher in the Lactate trial (3.0 vs 7.0 mmol×l-1, p<0.001) whereas muscle levels were only marginally higher (27 vs 32 mmol×kg-1 d.w., p=0.003) compared to the Saline-trial. Post-exercise blood pH was higher in the Lactate-trial (7.34 vs 7.44, p<0.001), with no differences in intramuscular pH. Exercise increased the phosphorylation of mTORS2448 (~40%), S6K1T389 (~3-fold), and p44T202/T204 (~80%) during recovery, without any differences between trials. FSR over the 24-h recovery period did not differ between the Saline (0.067 %/h) and Lactate (0.062 %/h) trials. This study does not support the hypothesis that blood lactate levels can modulate anabolic signaling in contracted human muscle. Further in vivo research investigating the impact of exercised versus rested muscle and the role of intramuscular lactate is needed to elucidate its potential signaling properties.
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| 31. |
- Lilja, Mats, et al.
(författare)
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Limited effect of over-the-counter doses of ibuprofen on mechanisms regulating muscle hypertrophy during resistance training in young adults.
- 2023
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 134:3, s. 753-765
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that maximal over-the-counter doses of ibuprofen, compared with low doses of acetylsalicylic acid, reduce muscle hypertrophy in young individuals after 8 weeks of resistance training. Because the mechanism behind this effect has not been fully elucidated, we here investigated skeletal muscle molecular responses and myofiber adaptations in response to acute and chronic resistance training with concomitant drug intake. Thirty-one young (aged 18-35 years) healthy men (n=17) and women (n=14) were randomized to receive either ibuprofen (IBU;1200mg daily; n=15) or acetylsalicylic acid (ASA; 75mg daily; n=16) while undergoing 8 weeks of knee extension training. Muscle biopsies from the vastus lateralis were obtained before, at week 4 after an acute exercise session, and after 8 weeks of resistance training and analyzed for mRNA markers and mTOR signaling, as well as quantification of total RNA content (marker of ribosome biogenesis) and immunohistochemical analyzes of muscle fiber size, satellite cell content, myonuclear accretion, and capillarization. There were only two treatment ´ time interaction in selected molecular markers after acute exercise (atrogin-1 and MuRF1 mRNA), but several exercise effects. Muscle fiber size, satellite cell and myonuclear accretion, and capillarization were not affected by chronic training or drug intake. RNA content increased comparably (~14%) in both groups. Collectively, these data suggest that established acute and chronic hypertrophy regulators (including mTOR signaling, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis) were not differentially affected between groups and therefore do not explain the deleterious effects of ibuprofen on muscle hypertrophy in young adults.
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| 32. |
- Moberg, Marcus, 1986-, et al.
(författare)
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Acute normobaric hypoxia blunts contraction-mediated mTORC1- and JNK-signaling in human skeletal muscle.
- 2022
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 234:2
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Hypoxia has been shown to reduce resistance exercise-induced stimulation of protein synthesis and long-term gains in muscle mass. However, the mechanism whereby hypoxia exerts its effect is not clear. Here we examine the effect of acute hypoxia on the activity of several signaling pathways involved in regulation of muscle growth following a bout of resistance exercise.METHODS: Eight men performed two sessions of leg resistance exercise in Normoxia or Hypoxia (12% O2 ) in a randomized crossover fashion. Muscle biopsies were obtained at rest and at 0, 90,180 min after exercise. Muscle analyses included levels of signaling proteins and metabolites associated with energy turnover.RESULTS: Exercise during Normoxia induced a 5-10-fold increase of S6K1Thr389 phosphorylation throughout the recovery period, but Hypoxia blunted the increases by ~50%. Phosphorylation of JNKThr183/Tyr185 and the JNK target SMAD2Ser245/250/255 was increased by 30-40-fold immediately after exercise in Normoxia, but Hypoxia blocked almost 70% of the activation. Throughout recovery, phosphorylation of JNK and SMAD2 remained elevated following exercise in Normoxia, but the effect of Hypoxia was lost at 90-180 min post-exercise. Hypoxia had no effect on exercise induced Hippo- or autophagy-signaling and ubiquitin-proteasome related protein levels. Nor did Hypoxia alter the changes induced by exercise in high energy phosphates, glucose 6-P, lactate, or phosphorylation of AMPK or ACC.CONCLUSION: We conclude that acute severe hypoxia inhibits resistance exercise induced mTORC1- and JNK signaling in human skeletal muscle, effects that do not appear to be mediated by changes in the degree of metabolic stress in the muscle.
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| 33. |
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| 34. |
- Moberg, Marcus, 1986-, et al.
(författare)
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High-intensity leg cycling alters the molecular response to resistance exercise in the arm muscles.
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- This study examined acute molecular responses to concurrent exercise involving different muscles. Eight men participated in a randomized crossover-trial with two sessions, one where they performed interval cycling followed by upper body resistance exercise (ER-Arm), and one with upper body resistance exercise only (R-Arm). Biopsies were taken from the triceps prior to and immediately, 90- and 180-min following exercise. Immediately after resistance exercise, the elevation in S6K1 activity was smaller and the 4E-BP1:eIF4E interaction greater in ER-Arm, but this acute attenuation disappeared during recovery. The protein synthetic rate in triceps was greater following exercise than at rest, with no difference between trials. The level of PGC-1α1 mRNA increased to greater extent in ER-Arm than R-Arm after 90 min of recovery, as was PGC-1α4 mRNA after both 90 and 180 min. Levels of MuRF-1 mRNA was unchanged in R-Arm, but elevated during recovery in ER-Arm, whereas MAFbx mRNA levels increased slightly in both trials. RNA sequencing in a subgroup of subjects revealed 862 differently expressed genes with ER-Arm versus R-Arm during recovery. These findings suggest that leg cycling prior to arm resistance exercise causes systemic changes that potentiate induction of specific genes in the triceps, without compromising the anabolic response.
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| 35. |
- Nilsson, Lina, et al.
(författare)
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Biphasic relationship between training load and glucose tolerance
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Biphasic relationship between training load and glucose tolerance Nilsson, L, Flockhart M, Bergman K, Apro W, Ekblom B, Larsen FJ There is a well-established construct regarding the positive effects of exercise on glucose tolerance and insulin sensitivity, as well as muscle glycogen storage. In insulin resistance, physical activity is an essential part of the treatment. However, the optimal dose is unknown. Reduced muscular glycogen stores, resulting from exercise, should stimulate an increased uptake of blood glucose. In this study we investigated the relation between training load, glucose tolerance and insulin sensitivity during three weeks of increasing interval training. Three times during the intervention, oral glucose tests were conducted to investigate the rate of glucose uptake. We found a biphasic dose-response relationship between training load and glucose tolerance, where an excessive training load led to a paradoxical reduction in glucose tolerance and impaired insulin release despite an unchanged amount of muscle glycogen. In light of these results, an upper limit of physical exercise exist where the negative effects overpowers the positive.
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| 36. |
- Nordström, Fabian, et al.
(författare)
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The lactate receptor GPR81 is predominantly expressed in type II human skeletal muscle fibers : potential for lactate autocrine signaling.
- 2023
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Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 324:2, s. C477-C487
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Tidskriftsartikel (refereegranskat)abstract
- GPR81 was first identified in adipocytes as a receptor for L-lactate, which upon binding inhibits cAMP-PKA-CREB signaling. Moreover, incubation of myotubes with lactate augments expression of GPR81 and genes and proteins involved in lactate- and energy metabolism. However, characterization of GPR81 expression and investigation of related signaling in human skeletal muscle under conditions of elevated circulating lactate levels are lacking. Muscle biopsies were obtained from healthy men and women at rest, after leg extension exercise, with or without venous infusion of sodium lactate, and 90 and 180 min after exercise (8 men and 8 women). Analyses included protein and mRNA levels of GPR81, as well as GPR81-dependent signaling molecules. GPR81 expression was 2.5-fold higher in type II glycolytic compared with type I oxidative muscle fibers, and the expression was inversely related to the percentage of type I muscle fibers. Muscle from women expressed about 25% more GPR81 protein than from men. Global PKA-activity increased by 5-8% after exercise, with no differences between trials. CREBS133 phosphorylation was reduced by 30% after exercise and remained repressed during the entire trials, with no influence of the lactate infusion. The mRNA expression of VEGF and PGC-1α were increased by 2.5 - 6-fold during recovery, and that of LDH reduced by 15% with no differences between trials for any gene at any time point. The high expression of GPR81-protein in type II fibers suggests that lactate functions as an autocrine signaling molecule in muscle; however, lactate does not appear to regulate CREB signaling during exercise.
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