Search

Abstract Knowledge of muscle contractile properties, physical fitness, and their associations with perceived fatigue may provide insights into mechanisms inducing fatigue and treatment targets. We aimed to identify differences in contractile properties and physical fitness between populations, and examine associations with perceived fatigue. We pooled data on perceived fatigue, physical fitness, and contractile properties from six studies, including a control group (n = 90), cancer survivors (n = 27), patients with chronic obstructive pulmonary disease (COPD; n = 16), chronic myeloid leukemia (CML; n = 20), and statin users (n = 64). We evaluated differences between populations, and associations of contractile properties and physical fitness with perceived fatigue. Compared with the control group, we found differences in contractile properties of patients with COPD (larger muscle force decline: β = −10.5%, 95% CI = −16.7; −4.2, increase in early relaxation time (Rt): β = 84.4%, 95% CI = 51.7; 117.0, increase in half Rt: β = 83.1%, 95% CI = 45.5; 120.7, muscle force rise (MFR): β = 0.2%/ms, 95% CI = 0.1; 0.3, and decrease in MFR: β = −24.3%, 95% CI = −35.7; −13.0) and statin users (early Rt: β = −5.4 ms, 95% CI = −10.0; −0.8, increase in early Rt: β = 19.8%, 95% CI = 2.5; 37.1). Associations between contractile properties and perceived fatigue varied across populations. Longer relaxation times were associated with higher perceived fatigue in hemato‐oncological populations. To conclude, contractile properties were impaired in patients with COPD and statin users. Associations between contractile properties and perceived fatigue varied across populations. In hemato‐oncological populations, impaired muscle relaxation was associated with higher perceived fatigue.

Abstract Drug-induced mitochondrial dysfunction is a common adverse effect, particularly in case of statins—the most prescribed drugs worldwide. These drugs have been shown to inhibit complex III (CIII) of the mitochondrial oxidative phosphorylation process, which is related to muscle pain. As muscle pain is the most common complaint of statin users, it is crucial to distinguish it from other causes of myalgia to prevent unnecessary cessation of drug therapy. However, diagnosing CIII inhibition currently requires muscle biopsies, which are invasive and not practical for routine testing. Less invasive alternatives for measurement of mitochondrial complex activities are only available yet for complex I and IV. Here, we describe a non-invasive spectrophotometric method to determine CIII catalytic activities using buccal swabs, which we validated in a cohort of statin and non-statin users. Our data indicate that CIII can be reliably measured in buccal swabs, as evidenced by reproducible results above the detection limit. Further validation on a large-scale clinical setting is recommended.

Volitional assessment of quadriceps muscle endurance is clinically relevant in patients with chronic obstructive pulmonary disease (COPD). However, studies that determine the construct validity of volitional tests by comparing them to non-volitional measures are lacking. Therefore, the aim of the current study is to evaluate the correlation between volitional and non-volitional quadriceps muscle endurance in patients with COPD. Quadriceps muscle endurance was evaluated in twenty-six patients with COPD. A volitional isometric and a volitional isokinetic protocol were performed on a computerised dynamometer to determine the isometric time and isokinetic work fatigue index, respectively. Non-volitional assessment of quadriceps muscle endurance was evaluated using repetitive electrical stimulations to establish the isometric muscle force decline. Sixteen patients (61 ± 8 years, 63% male, FEV1 47 (32–53)%) performed all three quadriceps endurance tests conforming to pre-defined test criteria. Both volitional isometric time and isokinetic work fatigue index did not significantly correlate with non-volitional muscle force decline (both p > 0.05). There was a strong correlation between volitional isometric time and isokinetic work fatigue index (rho = −0.716, p = 0.002). To conclude, this study suggests that volitional measures evaluate partly different aspects of quadriceps muscle endurance compared to non-volitional measures. Accordingly, these outcome measures cannot be used interchangeably.

Ketogenic diets and orally administered exogenous ketone supplements are strategies to increase serum ketone bodies serving as an alternative energy fuel for high energy demanding tissues, such as the brain, muscles, and the heart. The ketogenic diet is a low-carbohydrate and fat-rich diet, whereas ketone supplements are usually supplied as esters or salts. Nutritional ketosis, defined as serum ketone concentrations of ≥ 0.5 mmol/L, has a fasting-like effect and results in all sorts of metabolic shifts and thereby enhancing the health status. In this review, we thus discuss the different interventions to reach nutritional ketosis, and summarize the effects on heart diseases, epilepsy, mitochondrial diseases, and neurodegenerative disorders. Interest in the proposed therapeutic benefits of nutritional ketosis has been growing the past recent years. The implication of this nutritional intervention is becoming more evident and has shown interesting potential. Mechanistic insights explaining the overall health effects of the ketogenic state, will lead to precision nutrition for the latter diseases.

Abstract Background An inadequate protein intake may offset the muscle protein synthetic response after physical activity, reducing the possible benefits of an active lifestyle for muscle mass. We examined the effects of 12 weeks of daily protein supplementation on lean body mass, muscle strength, and physical performance in physically active older adults with a low habitual protein intake (

Abstract In non‐athletes, insulin sensitivity correlates negatively with intramyocellular lipid (IMCL) content. In athletes, however, a pattern of benign IMCL storage exists, which is characterized by lipid storage in type I muscle fibres, in small and numerous lipid droplets (LDs) preferable coated with PLIN5, without affecting insulin sensitivity. Administration of resveratrol has been promoted for its beneficial effects on glucose homeostasis. We observed that 30 days of oral resveratrol administration (150 mg/day) in metabolically compromised individuals showed a 33% increase in IMCL (placebo vs. resveratrol; 0.86 ± 0.090 AU vs. 1.14 ± 0.11 AU, p = 0.003) without impeding insulin sensitivity. Thus, the aim of the present study was to examine if a resveratrol‐mediated increase in IMCL content, in metabolically compromised individuals, changes the LD phenotype towards the phenotype we previously observed in athletes. For this, we studied IMCL, LD number, LD size, subcellular distribution and PLIN5 coating in different fibre types using high‐resolution confocal microscopy. As proof of concept, we observed a 2.3‐fold increase (p = 0.038) in lipid accumulation after 48 h of resveratrol incubation in cultured human primary muscle cells. In vivo analysis showed that resveratrol‐induced increase in IMCL is predominantly in type I muscle fibres (placebo vs. resveratrol; 0.97 ± 0.16% vs. 1.26 ± 0.09%; p = 0.030) in both the subsarcolemmal (p = 0.016) and intermyofibrillar region (p = 0.026) and particularly in PLIN5‐coated LDs (p = 0.024). These data indicate that administration of resveratrol augments IMCL content in metabolically compromised individuals towards a LD phenotype that mimics an ‘athlete like phenotype’.

Fatigue is a common side effect of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients. However, the prevalence of TKI-induced fatigue remains uncertain and little is known about predictors of fatigue and its relationship with physical activity. In this study, 220 CML patients receiving TKI therapy and 110 gender- and age-matched controls completed an online questionnaire to assess fatigue severity and fatigue predictors (Part 1). In addition, physical activity levels were objectively assessed for 7 consecutive days in 138 severely fatigued and non-fatigued CML patients using an activity monitor (Part 2). We demonstrated that the prevalence of severe fatigue was 55.5% in CML patients and 10.9% in controls (P

Skeletal muscle triglyceride accumulation is associated with insulin resistance in obesity. Recently, it has been suggested that α lipoic acid (ALA) improves insulin sensitivity by lowering triglyceride accumulation in nonadipose tissues via activation of skeletal muscle AMP-activated protein kinase (AMPK). We examined whether chronic ALA supplementation prevents muscular lipid accumulation that is associated with high-fat diets via activation of AMPK. In addition, we tested if ALA supplementation was able to improve insulin sensitivity in rats fed low- and high-fat diets (LFD, HFD). Supplementing male Wistar rats with 0.5% ALA for 8 weeks significantly reduced body weight, both on LFD and HFD (−24% LFD+ALA vs. LFD, P < 0.01, and −29% HFD+ALA vs. HFD, P < 0.001). Oil red O lipid staining revealed a 3-fold higher lipid content in skeletal muscle after HFD compared with LFD and ALA-supplemented groups (P < 0.05). ALA improved whole body glucose tolerance (∼20% lower total area under the curve (AUC) in ALA supplemented groups vs. controls, P < 0.05). These effects were not mediated by increased muscular AMPK activation or ALA-induced improvement of muscular insulin sensitivity. To conclude, the prevention of HFD-induced muscular lipid accumulation and the improved whole body glucose tolerance are likely secondary effects due to the anorexic nature of ALA.

BackgroundThe involvement of muscle triacylglycerol (TAG) storage in the onset of insulin resistance is questioned and the attention has shifted towards inhibition of insulin signalling by the lipid intermediate diacylglycerol (DAG). The enzyme 1,2-acylCoA:diacylglyceroltransferase-1 (DGAT1) esterifies a fatty acyl-CoA on DAG to form TAG. Therefore, the aim of the present study was to investigate if unilateral overexpression of DGAT1 in adult rat Tibialis anterior (TA) muscle will increase conversion of the lipid intermediate DAG into TAG, thereby improving muscle insulin sensitivity.Methodology/principal findingsThe DGAT1 gene construct was injected in the left TA muscle of male rats on chow or high-fat (45% kcal) diet for three weeks, followed by application of one 800 V/cm and four 80 V/cm pulses, using the contralateral leg as sham-electroporated control. Seven days after electroporation, muscle specific insulin sensitivity was assessed with a hyperinsulinemic euglycemic clamp using 2-deoxy-[3H]glucose. Here, we provide evidence that unilateral overexpression of DGAT1 in TA muscle of male rats is associated with an increased rather than decreased DAG content. Strikingly, this increase in DAG content was accompanied by improved muscle insulin sensitivity. Interestingly, markers of muscle lipolysis and mitochondrial function were also increased in DGAT1 overexpressing muscle.Conclusions/significanceWe conclude that unilateral DGAT1 overexpression can rescue insulin sensitivity, possibly by increasing DAG and TAG turnover in skeletal muscle. In case of a proper balance between the supply and oxidation of fatty acids in skeletal muscle, the lipid intermediate DAG may not exert harmful effects on insulin signalling.