Search

Revathy Munuswamy,1,* Jana De Brandt,2,* Chris Burtin,2 Wim Derave,3 Joseph Aumann,4 Martijn A Spruit,5,6,* Luc Michiels1,* 1Faculty of Medicine and Life Sciences, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 2Faculty of Rehabilitation Sciences, Rehabilitation Research Center REVAL, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 3Department of Movement and Sports Sciences, Ghent University, Ghent, Belgium; 4Department of Pneumology, Jessa Hospital, Hasselt, Belgium; 5Department of Research and Development, CIRO, Horn, the Netherlands; 6Department of Respiratory Medicine, Maastricht University Medical Centre, Faculty of Health, Medicine and Life Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands*These authors contributed equally to this workCorrespondence: Luc Michiels Email luc.michiels@uhasselt.beAbstract: Chronic low-grade systemic inflammation is frequently observed in patients with chronic obstructive pulmonary disease (COPD), e.g., elevated pentameric CRP (pCRP). However, pCRP can dissociate to form monomeric CRP (mCRP) which exhibits a clear pro-inflammatory behaviour in contrast to the more anti-inflammatory properties of pCRP. Therefore, mCRP may be an informative biomarker to demonstrate chronic low-grade systemic inflammation. This was confirmed by analysing serum samples from 38 patients with COPD and 18 non-COPD control persons (NCCP). mCRP was significantly elevated in patients with COPD vs. NCCP, indicating that mCRP might be considered as a new sensitive marker of chronic low-grade systemic inflammation.Keywords: COPD, low-grade systemic inflammation, pCRP, mCRP

Derave, W., B. F. Hansen, S. Lund, S. Kristiansen, and E. A. Richter. Muscle glycogen content affects insulin-stimulated glucose transport and protein kinase B activity. Am J Physiol Endocrinol Metab 279: E947-E955, 2000.--We investigated the possible regulatory role of glycogen in insulin-stimulated glucose transport and insulin signaling in skeletal muscle. Rats were preconditioned to obtain low (LG), normal, or high (HG) muscle glycogen content, and perfused isolated hindlimbs were exposed to 0, 100, or 10,000 [micro]U/ml insulin. In the fast-twitch white gastrocnemius, insulin-stimulated glucose transport was significantly higher in LG compared with HG. This difference was less pronounced in the mixed-fiber red gastrocnemius and was absent in the slow-twitch soleus. In the white gastrocnemius, insulin activation of insulin receptor tyrosine kinase and phosphoinositide 3-kinase was unaffected by glycogen levels, whereas protein kinase B activity was significantly higher in LG compared with HG. In additional incubation experiments on fast-twitch epitrochlearis muscles, insulin-stimulated cell surface GLUT-4 content was significantly higher in LG compared with HG. The data indicate that, in fast-twitch muscle, the effect of insulin on glucose transport and cell surface GLUT-4 content is modulated by glycogen content, which does not involve initial but possibly more downstream signaling events. GLUT-4; skeletal muscle; fiber type; phosphoinositide 3-kinase

Purpose: The molecular factors targeted by androgens and estrogens on muscle mass are not fully understood. The current study aimed to explore gene and protein expression of Atrogin-1, MuRF1, and myostatin in an androgen deprivation-induced muscle atrophy model. Methods: We examined the effects of Orx either with or without testosterone (T) or estradiol (E) administration on Atrogin-1 gene expression, and MuRF1 and myostatin gene and protein expression. Measurements were made in soleus (SOL), extensor digitorum longus (EDL) and levator ani/bulbocavernosus (LA/BC) of male C57BL/6 mice. Results: Thirty days of Orx resulted in a reduction in weight gain and muscle mass. These effects were prevented by T. In LA/BC, Atrogin-1 and MuRF1 mRNA was increased throughout 30 days of Orx, which was fully reversed by T and partially by E administration. In EDL and SOL, a less pronounced upregulation of both genes was only detectable at the early stages of Orx. Myostatin mRNA levels were downregulated in LA/BC and upregulated in EDL following Orx. T, but not E, reversed these effects. No changes in protein levels of MuRF1 and myostatin were found in EDL at any time point following Orx. Conclusions: The atrophy in SOL and EDL in response to androgen deprivation, and its restoration by T, is accompanied by only minimal changes in atrogenes and myostatin gene expression. The marked differences in muscle atrophy and atrogene and myostatin mRNA between LA/BC and the locomotor muscles suggest that the murine LA/BC is not an optimal model to study Orx-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3beta/4E-BP1, and muscle atrophy, including TNFalpha/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 +/- 0.2 years) and 16 older (70 +/- 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40-45% in the type II muscle fibers. TNFalpha and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3beta were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNFalpha, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although health-related benefits of fitness training in older men are well established, it is not clear yet which mode and intensity of a exercise program is most effective. This study addresses whether the combination of endurance (ED) and resistance training in older men have supplementary health-related benefits in addition to profits attained through endurance training alone. Additionally, effects of moderate- and low-intensity resistance training are compared. METHODS: Men, 55-75 years of age, were randomly assigned to a control group (N = 13) or one of three exercise groups (20 weeks, two to three times per week): endurance plus moderate resistance (MR) training (N = 22), endurance plus low resistance (LR) training (N = 22) and endurance training only (N = 22). Cardiovascular (CV) risk factors, muscular fitness and postural control were assessed before and after training. RESULTS: All exercise groups revealed significant (P < 0.05) improvements in resting heart rate, work capacity and recovery, waist girth, insulin response and knee-extensor strength with no differences among groups. Body composition, resting metabolic rate (RMR), VO2peak and postural control did not change in exercise groups. CONCLUSION: In older men, a fitness program consisting of 20 weeks endurance training combined with resistance training is equally effective as endurance training alone. Moderate vs. low resistance training added to endurance training yields similar health-related benefits. © 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Purpose: Human skeletal muscle has the profound ability to hypertrophy in response to resistance training (RT). However, this has a high energy and protein cost and is presumably mainly restricted to recruited muscles. It remains largely unknown what happens with nonrecruited muscles during RT. This study investigated the volume changes of 17 recruited and 13 nonrecruited muscles during a 10-wk single-joint RT program targeting upper arm and upper leg musculature., Methods: Muscle volume changes were measured by manual or automatic 3D segmentation in 21 RT novices. Subjects ate ad libitum during the study and energy and protein intake were assessed by self-reported diaries., Results: Posttraining, all recruited muscles increased in volume (range: +2.2% to +17.7%, P < 0.05), whereas the nonrecruited adductor magnus (mean: -1.5% ± 3.1%, P = 0.038) and soleus (-2.4% ± 2.3%, P = 0.0004) decreased in volume. Net muscle growth ( r = 0.453, P = 0.045) and changes in adductor magnus volume ( r = 0.450, P = 0.047) were positively associated with protein intake. Changes in total nonrecruited muscle volume ( r = 0.469, P = 0.037), adductor magnus ( r = 0.640, P = 0.002), adductor longus ( r = 0.465, P = 0.039), and soleus muscle volume ( r = 0.481, P = 0.032) were positively related to energy intake. When subjects were divided into a HIGH or LOW energy intake group, overall nonrecruited muscle volume (-1.7% ± 2.0%), adductor longus (-5.6% ± 3.7%), adductor magnus (-2.8% ± 2.4%), and soleus volume (-3.7% ± 1.8%) decreased significantly ( P < 0.05) in the LOW but not the HIGH group., Conclusions: To our knowledge, this is the first study documenting that some nonrecruited muscles significantly atrophy during a period of RT. Our data therefore suggest muscle mass reallocation, that is, that hypertrophy in recruited muscles takes place at the expense of atrophy in nonrecruited muscles, especially when energy and protein availability are limited., (Copyright © 2024 by the American College of Sports Medicine.)

Purpose: To gather information on practices and perceptions of high-performance experts regarding their athletes' muscle fiber-type composition (MFTC) and its estimation., Methods: A questionnaire on the noninvasive versus invasive estimation of MFTC was completed by 446 experts including coaches and sport-science/sports-medicine staff. Moreover, the perceived importance of MFTC for training and performance optimization was assessed. Differences between sport types (individual and team sports) were analyzed using chi-square tests., Results: Forty percent of the experts implemented MFTC assessment in pursuit of performance optimization, while 50% did not know their athletes' MFTC but expressed a desire to implement it if they would be able to assess MFTC. Ten percent did not perceive value in MFTC assessment. Only 18% of experts believed that their athletes would undergo a muscle biopsy, leading to the adoption of alternative noninvasive techniques. Experts primarily relied on their experience to estimate MFTC (65%), with experts working in individual sports using their experience more frequently than those working in team sports (68% vs 51%; P = .009). Jump tests emerged as the second-most commonly employed method for estimating MFTC (56%). When only considering experts who are currently using MFTC, 87% use MFTC to individualize training volume and 84% to individualize training intensity., Conclusions: Experts value MFTC assessment primarily to individualize training but mainly rely on noninvasive methods to estimate MFTC. Some of these methods lack scientific validity, suggesting a continuing need for education and further research in this area.

Purpose: Apnea duration is dependent on three factors: oxygen storage, oxygen consumption, hypoxia and hypercapnia tolerance. While current literature focuses on maximal apneas to improve apnea duration, apnea trained individuals use timed-repeated submaximal apneas, called "O 2 and CO 2 tables". These tables claim to accommodate the body to cope with hypoxia and hypercapnia, respectively. The aim of this study was twofold. First, to investigate the determinants of maximal apnea duration in apnea novices. Second, to compare physiologic responses to maximal apneas, O 2 and CO 2 tables., Methods: After medical screening, lung function test and hemoglobin mass measurement, twenty-eight apnea novices performed three apnea protocols in random order: maximal apneas, O 2 table and CO 2 table. During apnea, peripheral oxygen saturation (SpO 2 ), heart rate (HR), muscle (mTOI) and cerebral (cTOI) tissue oxygenation index were measured continuously. End-tidal carbon dioxide (EtCO 2 ) was measured before and after apneas., Results: Larger lung volumes, higher resting cTOI and lower resting EtCO 2 levels correlated with longer apnea durations. Maximal apneas induced greater decreases in SpO 2 (- 16%) and cTOI (- 13%) than O 2 (- 8%; - 8%) and CO 2 tables (- 6%; - 6%), whereas changes in EtCO 2 , HR and mTOI did not differ between protocols., Conclusion: These results suggest that, in apnea novices, O 2 and CO 2 tables did not induce a more profound hypoxia and hypercapnia, but a similar reduction in oxygen consumption than maximal apneas. Therefore, apnea novices should mainly focus on maximal apneas to improve hypoxia and hypercapnia tolerance. The use of specific lung training protocols can help to increase oxygen storage capacity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multiple intramuscular variables have been proposed to explain the high variability in resistance training induced muscle hypertrophy across humans. This study investigated if muscular androgen receptor (AR), estrogen receptor α (ERα) and β (ERβ) content and fiber capillarization are associated with fiber and whole-muscle hypertrophy after chronic resistance training. Male (n = 11) and female (n = 10) resistance training novices (22.1 ± 2.2 years) trained their knee extensors 3×/week for 10 weeks. Vastus lateralis biopsies were taken at baseline and post the training period to determine changes in fiber type specific cross-sectional area (CSA) and fiber capillarization by immunohistochemistry and, intramuscular AR, ERα and ERβ content by Western blotting. Vastus lateralis volume was quantified by MRI-based 3D segmentation. Vastus lateralis muscle volume significantly increased over the training period (+7.22%; range: -1.82 to +18.8%, p < 0.0001) but no changes occurred in all fiber (+1.64%; range: -21 to +34%, p = 0.869), type I fiber (+1.33%; range: -24 to +41%, p = 0.952) and type II fiber CSA (+2.19%; range: -23 to +29%, p = 0.838). However, wide inter-individual ranges were found. Resistance training increased the protein expression of ERα but not ERβ and AR, and the increase in ERα content was positively related to changes in fiber CSA. Only for the type II fibers, the baseline capillary-to-fiber-perimeter index was positively related to type II fiber hypertrophy but not to whole muscle responsiveness. In conclusion, an upregulation of ERα content and an adequate initial fiber capillarization may be contributing factors implicated in muscle fiber hypertrophy responsiveness after chronic resistance training., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Carnosine, an MR-visible dipeptide in human muscle, is well characterized by two peaks at ~8 and ~7 ppm from C2 and C4 imidazole protons. Like creatine and other metabolites, carnosine is subject to residual dipolar coupling in the anisotropic environment of muscle fibers, but the effects have not been studied extensively. Single-voxel TE 30-32 PRESS spectra from three different 3T studies were acquired from gastrocnemius medialis and soleus muscles in the human lower leg. In these studies, carnosine T 2 values were measured, and spectra were obtained at three different foot angles. LCModel was used to fit the carnosine peaks with a basis set that was generated using shaped RF pulses and included a range of dipolar couplings affecting the C4 peak. A seven-parameter analytic expression was used to fit the CH 2 doublets of creatine. It incorporated an optimized "effective TE" value to model the effect of shaped RF pulses. The fits confirm that the triplet C4 peak of carnosine is dipolar coupled to a pair of CH 2 protons, with no need to include a contribution from a separate pool of freely rotating uncoupled carnosine. Moreover, the couplings experienced by carnosine C4 protons and creatine CH 2 protons are strongly correlated (R 2  =  0.88, P<0.001), exhibiting a similar 3cos 2 θ - 1 dependence on the angle θ between fiber orientation and B0. T 2 values for the singlet C2 peak of gastrocnemius carnosine are inversely proportional to the C4 dipolar coupling strength (R 2  = 0.97, P < 0.001), which in turn is a function of foot orientation. This dependence indicates that careful positioning of the foot while acquiring lower leg muscle spectra is important to obtain reproducible carnosine concentrations. As proton magnetic resonance spectroscopy of carnosine is currently used to non-invasively estimate the muscle fiber typology, these results have important implications in sport science., (© 2024 John Wiley & Sons, Ltd.)

The wide variation in muscle fibre type distribution across individuals, along with the very different energy consumption rates in slow versus fast muscle fibres, suggests that muscle fibre typology contributes to inter-individual differences in metabolic rate during exercise. However, this has been hard to demonstrate due to the gap between a single muscle fibre and full-body exercises. We investigated the isolated effect of triceps surae muscle contraction velocity on whole-body metabolic rate during cyclic contractions in individuals a priori selected for their predominantly slow (n = 11) or fast (n = 10) muscle fibre typology by means of proton magnetic resonance spectroscopy ( 1 H-MRS). Subsequently, we examined their whole-body metabolic rate during walking and running at 2 m/s, exercises with comparable metabolic rates but distinct triceps surae muscle force and velocity demands (walking: low force, high velocity; running: high force, low velocity). Increasing triceps surae contraction velocity during cyclic contractions elevated net whole-body metabolic rate for both typology groups. However, the slow group consumed substantially less net metabolic energy at the slowest contraction velocity, but the metabolic difference between groups diminished at faster velocities. Consistent with the more economic force production during slow contractions, the slow group exhibited lower metabolic rates than the fast group while running, whereas metabolic rates were similar during walking. These findings provide important insights into the influence of muscle fibre typology on whole-body metabolic rate and emphasize the importance of considering muscle mechanical demands to understand muscle fibre typology related differences in whole-body metabolic rates. KEY POINTS: Muscle fibre typology is often suggested to affect whole-body metabolic rate, yet convincing in vivo evidence is lacking. Using isolated plantar flexor muscle contractions in individuals a priori selected for their predominantly slow or fast muscle fibre typology, we demonstrated that having predominantly slow muscle fibres provides a metabolic advantage during slow muscle contractions, but this benefit disappeared at faster contractions. We extended these results to full-body exercises, where we demonstrated that higher proportions of slow fibres associated with better economy during running but not when walking. These findings provide important insights into the influence of muscle fibre typology on whole-body metabolic rate and emphasize the importance of considering muscle mechanical demands to understand muscle fibre typology related differences in whole-body metabolic rate., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Muscle typology is heterogeneous among national level football (soccer) players, but positional differences remain unclear. Furthermore, fast typology (FT) individuals fatigue more than slow typology (ST) individuals in lab conditions. Therefore, we investigated if muscle typology is different between playing positions and if the decay in high-intensity activities from the first to the second half is larger in FT football players than in ST players. We estimated muscle typology in 147 male professional football players by measuring soleus and gastrocnemius muscle carnosine via proton magnetic resonance spectroscopy. Players were classified as ST, intermediate typology (IT) or FT and categorized as goalkeeper, center back, full back, midfielder, winger or forward. Across four seasons in-game distances covered in multiple running speed, acceleration and deceleration zones were collected during the first and second half. We found no differences in muscle typology between positions (p = 0.412). FT players covered 10.9% more high acceleration distance (>3 m.s -2 ) in the first half than ST players (p = 0.021) and high acceleration distance decay was larger for FT players (-12.4%) than ST (-7.7%; p = 0.006) and IT players (-7.3%; p = 0.010). Moreover, the decline in distance covered in several high-intensity zones tended to be larger in FT players (-11.2% high-intensity >15 km.h -1 ; -12.7% high deceleration <-3 m.s -2 ; -11.5% medium acceleration 2-3 m.s -2 ) than in ST players (-7.1% high-intensity; -8.1% high deceleration; -8.1% medium acceleration; 0.05 < p < 0.1). In conclusion, possessing a particular muscle typology is not required to play any football position at the national level. However, there are indications that FT players might fatigue more toward the end of the game compared to ST players., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Multiple sclerosis (MS) pathology features autoimmune-driven neuroinflammation, demyelination, and failed remyelination. Carnosine is a histidine-containing dipeptide (HCD) with pluripotent homeostatic properties that is able to improve outcomes in an animal MS model (EAE) when supplied exogenously. To uncover if endogenous carnosine is involved in, and protects against, MS-related neuroinflammation, demyelination or remyelination failure, we here studied the HCD-synthesizing enzyme carnosine synthase (CARNS1) in human MS lesions and two preclinical mouse MS models (EAE, cuprizone). We demonstrate that due to its presence in oligodendrocytes, CARNS1 expression is diminished in demyelinated MS lesions and mouse models mimicking demyelination/inflammation, but returns upon remyelination. Carns1-KO mice that are devoid of endogenous HCDs display exaggerated neuroinflammation and clinical symptoms during EAE, which could be partially rescued by exogenous carnosine treatment. Worsening of the disease appears to be driven by a central, not peripheral immune-modulatory, mechanism possibly linked to impaired clearance of the reactive carbonyl acrolein in Carns1-KO mice. In contrast, CARNS1 is not required for normal oligodendrocyte precursor cell differentiation and (re)myelin to occur, and neither endogenous nor exogenous HCDs protect against cuprizone-induced demyelination. In conclusion, the loss of CARNS1 from demyelinated MS lesions can aggravate disease progression through weakening the endogenous protection against neuroinflammation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To examine the association between muscle fiber typology and match running performance in professional Australian football (AF) athletes., Methods: An observational time-motion analysis was performed on 23 professional AF athletes during 224 games throughout the 2020 competitive season. Athletes were categorized by position as hybrid, small, or tall. Athlete running performance was measured using Global Navigation Satellite System devices. Mean total match running performance and maximal mean intensity values were calculated for moving mean durations between 1 and 10 minutes for speed (in meters per minute), high-speed-running distance (HSR, >4.17 m·s-1), and acceleration (in meters per second squared), while intercept and slopes were calculated using power law. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and expressed as a carnosine aggregate z score (CAZ score) to estimate muscle fiber typology. Mixed linear models were used to determine the association between CAZ score and running performance., Results: The mean (range) CAZ score was -0.60 (-1.89 to 1.25), indicating that most athletes possessed a greater estimated proportion of type I muscle fibers. A greater estimated proportion of type I fibers (ie, lower CAZ score) was associated with a larger accumulation of HSR (>4.17 m·s-1) and an increased ability to maintain HSR as the peak period duration increased., Conclusion: AF athletes with a greater estimated proportion of type I muscle fibers were associated with a greater capacity to accumulate distance running at high speeds, as well as a greater capacity to maintain higher output of HSR running during peak periods as duration increases.

This study examined whether muscle typology (muscle fibre type composition) is related to maximal strength and whether it can explain the high inter-individual variability in number of repetitions to failure during resistance training. Ninety-five resistance training novices (57 males) were assessed for their maximal isometric knee extension strength and muscle typology. Muscle typology was estimated by measuring carnosine in the soleus, gastrocnemius and/or vastus lateralis using proton magnetic resonance spectroscopy. Forty-four subjects (22 males) performed dynamic strength tests (1RM) and 3 sets of leg extensions and curls to failure (60%1RM) to determine the association between muscle typology and (total) number of repetitions. Twenty-one subjects performed additional biceps curls and triceps extensions (60%1RM) to assess influence of exercise, 23 subjects performed additional leg extensions and curls at 80% and 40%1RM to evaluate influence of training load. There was a weak but significant relationship between muscle typology and maximal isometric strength ( r  = 0.22, p  = 0.03) favouring the fast typology individuals. Slow and fast typology individuals did not differ in upper arm and upper leg 1RM. Total number of repetitions was related to muscle typology at 80% ( r  = -0.42; p  = 0.04) and 60% ( p  = -0.44; p  = 0.003) but not at 40%1RM. Slow typology individuals performed more repetitions to failure at 60%1RM in the leg extension ( p  = 0.03), leg curl ( p  = 0.01) and biceps curl ( p  = 0.02). In conclusion, muscle typology has a small contribution to maximal isometric strength but not dynamic strength and partly determines the number of repetitions to failure during resistance training. This insight can help individualizing resistance training prescriptions.

Aim: Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules with potent antioxidative and carbonyl quenching properties linked to various inflammatory, metabolic, and neurological diseases, as well as exercise performance. However, the distribution and metabolism of HCDs across tissues and species are still unclear., Methods: Using a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n = 26, n = 25, and n = 19 tissues, respectively)., Results: Our data show that tissue HCD levels are uniquely produced by carnosine synthase (CARNS1), an enzyme that was preferentially expressed by fast-twitch skeletal muscle fibres and brain oligodendrocytes. Cardiac HCD levels are remarkably low compared to other excitable tissues. Carnosine is unstable in human plasma, but is preferentially transported within red blood cells in humans but not rodents. The low abundant carnosine analogue N-acetylcarnosine is the most stable plasma HCD, and is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation, which is further induced by acute exercise in a myokine-like fashion., Conclusion: Collectively, we provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease., (© 2023 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)