Hyperglycemic diet and training alter insulin sensitivity, intramyocellular lipid content but not UCP3 protein expression in rat skeletal muscles

Intramyocellular lipids (IMCL) and mitochondrial uncoupling protein-3 (UCP3) have been implicated in the development of muscular insulin resistance. This study aimed to investigate the role of IMCL and UCP3 in the development of glucose intolerance and muscular insulin resistance during 12 weeks of an obesity-inducing 'cafeteria-style' diet alone (CAF), or in conjunction with exercise training from weeks 8-12 (CAFTR), in rats. At the end of the intervention period, gain in body weight was 20% higher in CAF (305+/-10 g) than controls (CON) (255+/-14 g; p<0.001) and CAFTR (253+/-7 g; p<0.001). Furthermore, compared with CON, the Matsuda insulin sensitivity index (ISI), assessed during a 2-h intravenous glucose tolerance test, was markedly lower in CAF (6.7+/-0.4) than in either CON (15.6+/-1.4; p<0.001) or CAFTR (11.2+/-1.1; p<0.001). Moreover, in CAF glucose transport at a submaximal insulin concentration (200 microU/ml) was reduced by approximately 60% (p<0.05) in both red and white gastrocnemius muscles, but not in m. soleus. However, glucose transport in CAFTR was similar to CON in red gastrocnemius. In CAF fiber-specific IMCL content determined in m. soleus and extensor digitorum longus (EDL), was higher than in CON (p<0.01) and CAFTR (p<0.001). Muscle UCP3 protein content was not changed by any of the interventions. Interestingly, within CAF and CAFTR, ISI closely negatively correlated with IMCL content in both type I (soleus, r=-0.93; EDL, r=-0.90; p<0.05) and IIa (EDL, r=-0.52, p<0.05) muscle fibers. These findings indicate that changes in IMCL content but not UCP3 content are implicated in short-term effects of cafeteria-style diet and exercise training on muscular insulin sensitivity in rats

Sedentary behaviour, physical activity and cardiometabolic health in highly trained athletes: A systematic review and meta-analysis

Prolonged periods of sedentary time appear to increase the risk for the development of several chronic conditions and all-cause mortality, even when moderate-to-vigorous physical activity (MVPA) is taken into consideration. However, whether the beneficial health effects of MVPA in highly active individuals remain present when leisure time is spent sedentary remains speculative. Therefore, we systematically evaluated off-training sedentary behaviour and physical activity levels in athletes. Studies were collected from four bibliographic databases (PubMed, Embase, Web of Science and The Cochrane Central Register of Controlled Trials). Studies were eligible for inclusion if they evaluated sedentary behaviour and physical activity levels among athletes. Data from athletes were compared with the general population and pooled using a random-effects model. After deduplication 3104 were identified of which 13 studies met inclusion criteria. Compared to the general population, athletes spent significantly more time in sedentary behaviour (+79 min/day; 95% confidence interval [CI]: [41, 65] min/day; p<0.001). In addition, athlete individuals spent less time in light intensity physical activity (-92 min/day; 95% CI: [-117, -66] min/day; p<0.001) and had increased levels of MVPA (+62 min/day; 95% CI: [38, 85] min/day; p<0.001) compared to the general population. Athletes exceed the average time spend sedentary per day and make them even more sedentary compared to the general population

Sedentary behaviour, physical activity and cardiometabolic health in highly trained athletes: A systematic review and meta-analysis

Prolonged periods of sedentary time appear to increase the risk for the development of several chronic conditions and all-cause mortality, even when moderate-to-vigorous physical activity (MVPA) is taken into consideration. However, whether the beneficial health effects of MVPA in highly active individuals remain present when leisure time is spent sedentary remains speculative. Therefore, we systematically evaluated off-training sedentary behaviour and physical activity levels in athletes. Studies were collected from four bibliographic databases (PubMed, Embase, Web of Science and The Cochrane Central Register of Controlled Trials). Studies were eligible for inclusion if they evaluated sedentary behaviour and physical activity levels among athletes. Data from athletes were compared with the general population and pooled using a random-effects model. After deduplication 3104 were identified of which 13 studies met inclusion criteria. Compared to the general population, athletes spent significantly more time in sedentary behaviour (+79 min/day; 95% confidence interval [CI]: [41, 65] min/day; p<0.001). In addition, athlete individuals spent less time in light intensity physical activity (-92 min/day; 95% CI: [-117, -66] min/day; p<0.001) and had increased levels of MVPA (+62 min/day; 95% CI: [38, 85] min/day; p<0.001) compared to the general population. Athletes exceed the average time spend sedentary per day and make them even more sedentary compared to the general population

Is maximal muscle strength and fatigability of three lower limb muscle groups associated with walking capacity and fatigability in multiple sclerosis? An exploratory study

Background: Both muscle fatigability and walking fatigability are prevalent in persons with MS (pwMS), but their associations remains unclear. The aim of this study was to examine the association of muscle strength and fatigability from both isometric and concentric protocols of three different muscle groups, and their association to walking capacity and walking fatigability.Methods: Twenty-seven pwMS and 13 Healthy Controls (HC) were included in this exploratory study. All par-ticipants performed a six-minute walking test (6MWT), where the distance walked index (DWI) was calculated to measure walking fatigability with a cut-off score of-10%. In three different muscle groups (knee extensors (KE), knee flexors (KF), ankle dorsiflexors (DF)), isometric and concentric muscle fatigability protocols (FIisometric or FIconcentric) were used to quantify maximal voluntary contraction (MVC) and muscle fatigability. Pearson or Spearman correlation coefficients and linear regression models were calculated to establish the association be-tween muscle strength/fatigability and walking capacity/fatigability.Results: Higher MVCs values for all muscle groups were found in HC compared to pwMS (mainly those having walking fatigability) (p < 0.05). FIisometric of DF was lower in pwMS having walking fatigability compared to no walking fatigability. MVC of KE, KF and DF had a low to moderate association with walking capacity (range r = 0.52-0.56; p < 0.05) and walking fatigability in pwMS (range r-r(s): 0.39-0.50; p<0.05). FIconcentric of KF and DF, but not of KE, were associated with walking fatigability (r = 0.39 and rs = 0.47, respectively; p < 0.05). In contrast, FIisometric for all muscle groups were not related to walking capacity or walking fatigability.Conclusion: MVC of KE, KF and DF are associated with walking capacity and walking fatigability, while concentric (but not isometric) muscle fatigability of KF and DF are associated with walking fatigability

Carnosine and skeletal muscle dysfunction in a rodent multiple sclerosis model

Muscle weakness and fatigue are primary manifestations of multiple sclerosis (MS), a chronic disease of the central nervous system. Interventions that enhance muscle function may improve overall physical well-being of MS patients. Recently, we described that levels of carnosine, an endogenous muscle dipeptide involved in contractile function and fatigue-resistance, are reduced in muscle tissue from MS patients and a monophasic rodent MS model (experimental autoimmune encephalomyelitis, EAE). In the present study, we aimed to (1) confrm this fnding in a chronic EAE model, along with the characterization of structural and functional muscle alterations, and (2) investigate the efect of carnosine supplementation to increase/restore muscle carnosine levels and improve muscle function in EAE. We performed muscle immunohistochemistry and ex vivo contractility measurements to examine muscle structure and function at diferent stages of EAE, and following nutritional intervention (oral carnosine: 3, 15 or 30 g/L in drinking water). Immunohistochemistry revealed progressively worsening muscle fber atrophy and a switch towards a fast-twitch muscle phenotype during EAE. Using ex vivo muscle contractility experiments, we observed reductions in muscle strength and contraction speed, but no changes in muscle fatigability of EAE mice. However, carnosine levels were unaltered during all stages of EAE, and even though oral carnosine supplementation dose-dependently increased muscle carnosine levels up to+94% after 56 days EAE, this did not improve muscle function of EAE mice. In conclusion, EAE mice display signifcant, yet time-dependent, muscular alterations, and carnosine intervention does not improve muscle function in EAE

Carnosine quenches the reactive carbonyl acrolein in the central nervous system and attenuates autoimmune neuroinflammation

Background: Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation.Methods: The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes).Results: Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (beta-alanyl-l-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were similar to twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects.Conclusions: Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS

Carnosine quenches the reactive carbonyl acrolein in the central nervous system and attenuates autoimmune neuroinflammation

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease driven by sustained inflammation in the central nervous system. One of the pathological hallmarks of MS is extensive free radical production. However, the subsequent generation, potential pathological role, and detoxification of different lipid peroxidation-derived reactive carbonyl species during neuroinflammation are unclear, as are the therapeutic benefits of carbonyl quenchers. Here, we investigated the reactive carbonyl acrolein and (the therapeutic effect of) acrolein quenching by carnosine during neuroinflammation. METHODS: The abundance and localization of acrolein was investigated in inflammatory lesions of MS patients and experimental autoimmune encephalomyelitis (EAE) mice. In addition, we analysed carnosine levels and acrolein quenching by endogenous and exogenous carnosine in EAE. Finally, the therapeutic effect of exogenous carnosine was assessed in vivo (EAE) and in vitro (primary mouse microglia, macrophages, astrocytes). RESULTS: Acrolein was substantially increased in inflammatory lesions of MS patients and EAE mice. Levels of the dipeptide carnosine (β-alanyl-l-histidine), an endogenous carbonyl quencher particularly reactive towards acrolein, and the carnosine-acrolein adduct (carnosine-propanal) were ~ twofold lower within EAE spinal cord tissue. Oral carnosine treatment augmented spinal cord carnosine levels (up to > tenfold), increased carnosine-acrolein quenching, reduced acrolein-protein adduct formation, suppressed inflammatory activity, and alleviated clinical disease severity in EAE. In vivo and in vitro studies indicate that pro-inflammatory microglia/macrophages generate acrolein, which can be efficiently quenched by increasing carnosine availability, resulting in suppressed inflammatory activity. Other properties of carnosine (antioxidant, nitric oxide scavenging) may also contribute to the therapeutic effects. CONCLUSIONS: Our results identify carbonyl (particularly acrolein) quenching by carnosine as a therapeutic strategy to counter inflammation and macromolecular damage in MS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02306-9