Exercise metabolism in non-obese patients with type 2 diabetes following the acute restoration of normoglycaemia

This study investigated how acute restoration of normoglycaemia affected energy metabolism during exercise in nonobese patients with type 2 diabetes. Six subjects (mean ± SEM) aged 56.2 ± 2.7 years, with a BMI of 24.5 ± 1.5 kg/m2 and a VO2 peak of 28.7 ml/kg/min, attended the lab on two randomised occasions for a four-hour resting infusion of insulin or saline, followed by 30 minutes cycling at 50% VO2 peak. During the 4 h resting infusion, there was a greater (P < 0 0001) reduction in blood glucose in insulin treatment (INS) (from 11.2 ± 0.6 to 5.6 ± 0.1 mmol/l) than in saline treatment/control (CON) (from 11.5 ± 0.7 to 8.5 ± 0.6 mmol/l). This was associated with a lower (P < 0 05) resting metabolic rate in INS (3.87 ± 0.17) than in CON (4.39 ± 0.30 kJ/min). During subsequent exercise, blood glucose increased significantly in INS from 5.6 ± 0.1 at 0 min to 6.3 ± 0.3 mmol/l at 30 min (P < 0 01), which was accompanied by a lower blood lactate response (P < 0 05). Oxygen uptake, rates of substrate utilization, heart rate, and ratings of perceived exertion were not different between trials. Insulin-induced normoglycaemia increased blood glucose during subsequent exercise without altering overall substrate utilization

IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development

Studies in murine cell lines and in mouse models suggest that IL-15 promotes myogenesis and may protect against the inflammation-mediated skeletal muscle atrophy which occurs in sarcopenia and cachexia. The effects of IL-15 on human skeletal muscle growth and development remain largely uncharacterised. Myogenic cultures were isolated from the skeletal muscle of young and elderly subjects. Myoblasts were differentiated for 8 d, with or without the addition of recombinant cytokines (rIL-15, rTNFα) and an IL-15 receptor neutralising antibody. Although myotubes were 19% thinner in cultures derived from elderly subjects, rIL-15 increased the thickness of myotubes (MTT) from both age groups to a similar extent. Neutralisation of the high-affinity IL-15 receptor binding subunit, IL-15rα in elderly myotubes confirmed that autocrine concentrations of IL-15 also support myogenesis. Co-incubation of differentiating myoblasts with rIL-15 and rTNFα, limited the reduction in MTT and nuclear fusion index (NFI) associated with rTNFα stimulation alone. IL-15rα neutralisation and rTNFα decreased MTT and NFI further. This, coupled with our observation that myotubes secrete IL-15 in response to TNFα stimulation supports the notion that IL-15 serves to mitigate inflammatory skeletal muscle loss. IL-15 may be an effective therapeutic target for the attenuation of inflammation-mediated skeletal muscle atrophy

Skeletal muscle myostatin mRNA expression is upregulated in aged human adults with excess adiposity, but is not associated with insulin resistance and ageing

Myostatin negatively regulates skeletal muscle growth and appears upregulated in human obesity and associated with insulin resistance. However, observations are confounded by ageing, and the mechanisms responsible are unknown. The aim of this study was to delineate between the effects of excess adiposity, insulin resistance and ageing on myostatin mRNA expression in human skeletal muscle and to investigate causative factors using in vitro models. An in vivo cross-sectional analysis of human skeletal muscle was undertaken to isolate effects of excess adiposity and ageing per se on myostatin expression. In vitro studies employed human primary myotubes to investigate the potential involvement of cross-talk between subcutaneous adipose tissue (SAT) and skeletal muscle, and lipid-induced insulin resistance. Skeletal muscle myostatin mRNA expression was greater in aged adults with excess adiposity than age-matched adults with normal adiposity (2.0-fold higher; P &lt; 0.05) and occurred concurrently with altered expression of genes involved in the maintenance of muscle mass but did not differ between younger and aged adults with normal adiposity. Neither chronic exposure to obese SAT secretome nor acute elevation of fatty acid availability (which induced insulin resistance) replicated the obesity-mediated upregulation of myostatin mRNA expression in vitro. In conclusion, skeletal muscle myostatin mRNA expression is uniquely upregulated in aged adults with excess adiposity and insulin resistance but not by ageing alone. This does not appear to be mediated by the SAT secretome or by lipid-induced insulin resistance. Thus, factors intrinsic to skeletal muscle may be responsible for the obesity-mediated upregulation of myostatin, and future work to establish causality is required

Reduced skeletal muscle protein balance in paediatric Crohn’s disease

Background and AimsAn inability to respond to nutrition could be implicated in low muscle mass in Crohn’s disease. We aim to determine skeletal muscle metabolic response to feeding in Crohn’s disease and healthy volunteers.MethodsTwenty asymptomatic Crohn’s disease participants (15.6 ± 0.5 yrs; BMI 20.6 ± 0.9 kg/m2); 9 with active disease (faecal calprotectin, 808 ± 225ug/g and C-reactive protein, 2.2 ± 1.2 mg/dl), 11 in deep remission (faecal calprotectin, 61 ± 12ug/g and C-reactive protein, 0.3 ± 0.2 mg/dl) and 9 matched healthy volunteers (16.0±0.6 yrs; BMI 20.7±0.6 kg/m2) were recruited. Participants had a dual energy X-ray absorptiometry scan, handgrip dynamometer test, wore a pedometer and completed a food diary. Arterialised hand and venous forearm blood samples were collected concurrently and brachial artery blood flow measured at baseline and every 20mins for 2hrs after the ingestion of a standardised liquid meal. Net balance of branched chain amino acids and glucose were derived.ResultsControls had a positive mean BCAA balance. CD participants had an initial anabolic response to the meal, with increasing BCAA balance between t=0 & t=20, but returned to negative by t=60. This was associated with reduced FFM z-scores in CD but not with insulin resistance or disease activity. Exploratory analyses suggest that negative postprandial BCAA response seen in CD is predominant in males (p=0.049), with associated lower appendicular muscle mass (p=0.034), higher muscle fatigue (p=0.014) and reduced protein intake (p=0.026).ConclusionsThe inability to sustain a positive protein balance postprandially could provide an explanation for the reduced muscle mass seen in CD. Further mechanistic studies will be needed to confirm these findings

Going Back to the Biology of FGF21: New Insights

© 2019 Elsevier Ltd Fibroblast growth factor 21 (FGF21) is a protein highly synthesized in the liver that exerts paracrine and endocrine control of many aspects of energy homeostasis in multiple tissues. In preclinical models of obesity and type 2 diabetes, treatment with FGF21 improves glucose homeostasis and promotes weight loss, and, as a result, FGF21 has attracted considerable attention as a therapeutic agent for the treatment of metabolic syndrome in humans. An improved understanding of the biological role of FGF21 may help to explain why its therapeutic potential in humans has not been fully realized. This review will cover the complexities in FGF21 biology in rodents and humans, with emphasis on its role in protection from central and peripheral facets of obesity

Minimizing sedentary behavior (without increasing medium-to-vigorous exercise) associated functional improvement in older women is somewhat dependent on a measurable increase in muscle size.

The optimal pattern of sedentarism displacement and mechanisms underlying its health effects are poorly understood. Therefore, the aim of this study was to quantify muscle-tendon adaptation in response to two different sedentarism displacement interventions and relate any adaptations to functional outcomes. Thirty-four older women (73±5yrs) underwent skeletal muscle-tendon size and functional assessments. Participants were randomly allocated to: Sedentary behaviour fragmentation (SBF), Light intensity physical activity (LIPA), or Control groups. Measures were taken at weeks 0 and 8. Gait speed significantly increased (p=0.003), in both experimental groups (SBF: 0.06 ± 0.08m/s, 6±10%, LIPA: 0.06 ± 0.07m/s, 6±6%), but not control (-0.02 ± 0.12m/s, -2±9%). Accordingly, the relative change in Vastus Lateralis muscle volume, accounted for 30% (p=0.027), and 45% (p=0.0006) of the explained variance in the relative change in gait speed, for SBF and LIPA respectively. Gastrocnemius Medialis fascicle length changes were positively associated with gait speed changes, following LIPA exclusively (R2= 0.50, p=0.009). This is the first study to show SBF and LIPA are adequate loading in older women, with related muscle adaptation and clinically relevant gait speed improvements. Such adaptations appear similar irrespective of whether sedentarism displacement is prescribed in a single bout (LIPA) or in frequent micro-bouts (SBF)

The Effects of Displacing Sedentary Behavior With Two Distinct Patterns of Light Activity on Health Outcomes in Older Adults (Implications for COVID-19 Quarantine)

Rationale: The COVID-19 pandemic is limiting outdoor and community-based activities, especially for older adults owing to the requirement for self-isolation, potentially increasing prolonged sedentary behavior (SB). Given a poor tolerance for intense exercise, SB displacement with light intensity physical activity (LIPA) is a promising health enhancing alternative. Therefore, the aims of this study were to investigate the effects of two different types of SB displacement on health outcomes in older adults and any differential impact of associated LIPA pattern. Method: 28 older women (age: 73 ± 5 years, height: 1.60 ± 0.07 m, weight: 67 ± 10 kg, and BMI: 26.1 ± 3.6 kg/m2) underwent overnight fasted dual energy x-ray absorptiometry (DEXA) imaging, blood sampling, and functional assessments before being randomly allocated to one of two groups: (1) single continuous bout of 45–50 min LIPA daily (n = 14); or (2) SB fragmentation (SBF; ~48 min LIPA daily, 2 min LIPA for every 30 min of SB; n = 14). Compliance was systematically monitored using tri-axial accelerometery. All measures were taken at weeks 0 and 8. Results: Physical behavior significantly altered (decreased SB/increased LIPA; p < 0.05) and to a similar extent in both groups. We observed a significant reduction in serum triglycerides [p = 0.045, effect size (ɳp2) = 0.15; SBF: −0.26 ± 0.77 mmol/L, LIPA: −0.26 ± 0.51 mmol/L], improved 30 s sit-to-stand (STS) count (p = 0.002, ɳp2 = 0.32, 2 ± 3 STS) and speed (p = 0.009, ɳp2 = 0.35, −10 ± 33%), as well as increased average handgrip strength (p = 0.001, ɳp2 = 0.45, 6 ± 12%), and gait speed (p = 0.005, ɳp2 = 0.27, 0.09 ± 0.16 m/s) in both groups. Interestingly, SBF caused a greater increase in peak handgrip strength (8 ± 14%), compared to LIPA (2 ± 10%; p = 0.04, ɳp2 = 0.38). Conclusion: SB displacement induced significant improvements in fasting triglycerides, gait speed, as-well as STS endurance/speed in older women. Frequent vs. continuous SB displacement also caused greater increases in handgrip strength. While both SB displacement protocols display promise as efficacious home-based interventions for self-isolating older adults, our results would suggest a physical functioning advantage of the SBF protocol for certain outcomes

Exploring mechanisms of fatigue during repeated exercise and the dose dependent effects of carbohydrate and protein ingestion:study protocol for a randomised controlled trial

BACKGROUND: Muscle glycogen has been well established as the primary metabolic energy substrate during physical exercise of moderate- to high-intensity and has accordingly been implicated as a limiting factor when such activity is sustained for a prolonged duration. However, the role of this substrate during repeated exercise after limited recovery is less clear, with ongoing debate regarding how recovery processes can best be supported via nutritional intervention. The aim of this project is to examine the causes of fatigue during repeated exercise bouts via manipulation of glycogen availability through nutritional intervention, thus simultaneously informing aspects of the optimal feeding strategy for recovery from prolonged exercise. METHODS/DESIGN: The project involves two phases with each involving two treatment arms administered in a repeated measures design. For each treatment, participants will be required to exercise to the point of volitional exhaustion on a motorised treadmill at 70% of previously determined maximal oxygen uptake, before a four hour recovery period in which participants will be prescribed solutions providing 1.2 grams of sucrose per kilogram of body mass per hour of recovery (g.kg(-1).h(-1)) relative to either a lower rate of sucrose ingestion (that is, 0.3 g.kg(-1). h(-1); Phase I) or a moderate dose (that is, 0.8 g.kg(-1).h(-1)) rendered isocaloric via the addition of 0.4 g.kg(-1).h(-1) whey protein hydrolysate (Phase II); the latter administered in a double blind manner as part of a randomised and counterbalanced design. Muscle biopsies will be sampled at the beginning and end of recovery for determination of muscle glycogen resynthesis rates, with further biopsies taken following a second bout of exhaustive exercise to determine differences in substrate availability relative to the initial sample taken following the first exercise bout. DISCUSSION: Phase I will inform whether a dose–response relationship exists between carbohydrate ingestion rate and muscle glycogen availability and/or the subsequent capacity for physical exercise. Phase II will determine whether such effects are dependent on glycogen availability per se or energy intake, potentially via protein mediated mechanisms. TRIAL REGISTRATION: ISRCTN87937960