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Skeletal muscle IL-15/IL-15Rα and myofibrillar protein synthesis after resistance exercise

Posted by J.McKendry, M.Martin-Rincon, D.Morales-Alamo, et al. on 2017-06-08 00:05:06


In vitro and in vivo studies described the myokine IL-15 and its receptor IL-15Rα as anabolic/anti-atrophy agents, however, the protein expression of IL-15Rα has not been measured in human skeletal muscle and data regarding IL-15 expression remain inconclusive. The purpose of the study was to determine serum and skeletal muscle IL-15 and IL-15Rα responses to resistance exercise session and to analyze their association with myofibrillar protein synthesis (MPS). Fourteen participants performed a bilateral leg resistance exercise composed of four sets of leg press and four sets of knee extension at 75% 1RM to task failure. Muscle biopsies were obtained at rest, 0, 4 and 24 hours post-exercise and blood samples at rest, mid-exercise, 0, 0.3, 1, 2, 4 and 24 hours post-exercise. Serum IL-15 was increased by ~5.3-fold immediately post-exercise, while serum IL-15Rα decreased ~75% over 1 hour post-exercise (P<.001). Skeletal muscle IL-15Rα mRNA and protein expression were increased at 4 hours post-exercise by ~2-fold (P<.001) and ~1.3-fold above rest (P=.020), respectively. At 24 hours post-exercise, IL-15 (P=.003) and IL-15Rα mRNAs increased by ~2-fold (P=.002). Myofibrillar fractional synthetic rate between 0-4 hours was associated with IL-15Rα mRNA at rest (r=.662, P=.019), 4 hours (r=.612, P=.029), and 24 hours post-exercise (r=.627, P=.029). Finally, the muscle IL-15Rα protein up-regulation was related to Leg press 1RM (r=.688, P=.003) and total weight lifted (r=.628, P=.009). In conclusion, IL-15/IL-15Rα signaling pathway is activated in skeletal muscle in response to a session of resistance exercise.



We aimed to assess the prevalence of autoantibodies against the 4A subunit of the gastric proton pump (ATP4A) in pediatric type 1 diabetes (T1D) patients and explore the relationship between ATP4A positivity and blood cell count, iron turnover, and vitamin B12 concentration.


The study included 94 (59% female) T1D children (aged 12.5 ± 4.1 years, T1D duration 4.2 ± 3.6 years, HbA1c 7.3 ± 1.5% (57 ± 12.6 mmol/mol) with no other autoimmune diseases.


ATP4A antibodies were measured in T1D patients using a radioimmunoprecipitation assay. Blood cell count, iron concentration, total iron binding capacity, ferritin, transferrin, hepcidin, and vitamin B12 concentration were measured in all the study participants.


A total of 16 (17%) children were ATP4A positive. Serum concentrations of ferritin were significantly lower in ATP4A positive than in antibody negative subjects (P = .034). Overall the levels of ATP4A antibodies (ATP4A Index) correlated positively with the age at T1D diagnosis (r = 0.228, P = .026) and negatively with ferritin levels (r = −0.215, P = .037). In ATP4A positive patients, the ATP4A Index correlated positively with age at diagnosis (r = 0.544, P = .032) and negatively with vitamin B12 levels (r = −0.685, P = .004).


ATP4A antibodies were present in a significant proportion of children with T1D. Higher ATP4A levels in T1D children are associated with lower, yet still fitting within the normal range, levels of vitamin B12, and ferritin. Routine screening of T1D children for gastric autoimmunity (ATP4A) should be considered with follow-up of those positive for vitamin B12 and iron deficiency.

5-azacytidine mediated hMSC behaviour on electrospun scaffolds for skeletal muscle regeneration

Posted by Ines F, Vincenzo G, Valentina C, et al. on 2017-06-07 20:02:15


Incomplete regeneration after trauma or muscular dysfunction is a common problem in muscle replacement therapies. Recent approaches in tissue engineering allow for the replication of skeletal muscle structure and function in vitro and in vivo by molecular therapies and implantable scaffolds which properly address muscle cells towards myotube differentiation and maturation. Here, we investigate the in vitro response of human Mesenchymal Stem Cells (hMSC) on electrospun fibres made of Polycaprolactone (PCL) in the presence of 5-azacytidine (5-AZA) to evaluate how fibrous network may influence the therapeutic effect of drug during in vitro myogenesis. Biological studies demonstrate the ability of hMSCs to differentiate in mature myofibres in supplemented (myogenic) and, preferentially, in 5-AZA enriched culture. PCL electrospun fibres amplify the 5-AZA capability to induce a low proliferation rate in hMSC thus promoting hMSC differentiation (MTT assay). Qualitative (Azan Mallory stain, immunofluorescence assay, SEM analyses) and quantitative (ELISA test) assays confirm the synergistic contribution of PCL electrospun fibres and 5-AZA on in vitro myotubes formation and maturation. This result is also confirmed by the expression of muscle specific proteins related to the myogenic mechanisms in the presence of other muscle inductive signals (i.e., oxytocin, Tweak). Hence, we suggest the use of PCL electrospun fibres as interesting preclinical model to explore the effect of drugs and chemotherapeutics administration after damaged muscle resection. This article is protected by copyright. All rights reserved.

ANGPTL8 (Betatrophin) is Expressed in Visceral Adipose Tissue and Relates to Human Hepatic Steatosis in Two Independent Clinical Collectives

Posted by Christian von L, Andreas F. H. Pfeiffer, Johan F. L, et al. on 2017-06-07 19:23:22

Angiopoietin-like protein 8 (ANGPTL8)/betatrophin expression in visceral adipose tissue and associations with circulating fatty acid profile have not yet been investigated. Forty subjects were included in a cross-sectional study, 57 in a dietary weight reduction intervention. Circulating Angiopoietin-like protein 8/betatrophin was measured in all subjects. Liver and adipose tissue were sampled and plasma fatty acids and tissue Angiopoietin-like protein 8/betatrophin expression were evaluated in the cross-sectional study. In the intervention study oral glucose testing and liver magnetic resonance scanning at baseline and after 6 months were performed. Angiopoietin-like protein 8/betatrophin mRNA was increased in visceral compared to subcutaneous adipose tissue (p < 0.001). Circulating ANGPTL8/betatrophin correlated with liver steatosis (r = 0.42, p = 0.047), triacylglycerols (r = 0.34, p = 0.046), saturated (r = 0.43, p = 0.022), monounsaturated (r = 0.51, p = 0.007), and polyunsaturated fatty acids (r = − 0.53, p = 0.004).In the intervention study, baseline Angiopoietin-like protein 8/betatrophin correlated with age (r = 0.32, p = 0.010) and triacylglycerols (r = 0.30, p = 0.02) and was increased with hepatic steatosis (p = 0.033). Weight loss reduced liver fat by 45 % and circulating Angiopoietin-like protein 8/betatrophin by 11 % (288 ± 17 vs. 258 ± 17 pg/ml; p = 0.015). Angiopoietin-like protein 8/betatrophin is related to liver steatosis, while visceral adipose tissue represents an additional site of expression in humans.

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n = 220) with a body mass index (BMI) < 27 kg/m2. Subjects were categorized as normoglycemic (n = 55), IFG (n = 50), IGT (n = 60), and DM (n = 55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p < 0.005), IFG (p < 0.004), and IGT (p < 0.001). Male subjects have significantly higher betatrophin levels than female subjects (p < 0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p < 0.04), IFG (p < 0.01), and IGT (p < 0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages.

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