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Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise.

ABSTRACT: Recent findings regarding the response of fibronectin type III domain-containing protein 5 (Fndc5) and irisin to exercise are partly controversial. While the 25 kDa form of Fndc5 can be observed in muscle and serum of different species, the ~12 kDa irisin band was not detectable up to now. The present study aimed to clarify whether irisin exists in its theoretical size of ~12 kDa in mice and if it is affected by exercise. Male mice were randomly assigned to a sedentary control group (CO), a group with free access to running wheels (RW), and a treadmill group (TM). Blood and leg muscles were collected to investigate the regulatory cascade including peroxisome proliferator-activated receptor gamma co-activator 1-alpha (Ppargc1a) and Fndc5. In western blot analysis, antibodies were used capable of differentiation between full-length Fndc5 and irisin. This enabled us to demonstrate that irisin exists in muscle and serum of mice independent of exercise and that it is increased immediately after acute exercise. Different transcripts of Ppargc1a mRNA, but not Fndc5 mRNA, were up-regulated in the TM group. Furthermore, neither Fndc5 (25 kDa) nor Ppargc1a protein was elevated in muscle tissue. The Ppargc1a-Fndc5/irisin pathway did not clearly respond to mild exercise in the RW group. Our results provide evidence for the existence of irisin and for its immediate response to acute exercise in mice.

SUBMITTER: Brenmoehl J

PROVIDER: S-EPMC3957089 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise.

Brenmoehl Julia J Albrecht Elke E Komolka Katrin K Schering Lisa L Langhammer Martina M Hoeflich Andreas A Maak Steffen S

International journal of biological sciences 20140311 3

Recent findings regarding the response of fibronectin type III domain-containing protein 5 (Fndc5) and irisin to exercise are partly controversial. While the 25 kDa form of Fndc5 can be observed in muscle and serum of different species, the ~12 kDa irisin band was not detectable up to now. The present study aimed to clarify whether irisin exists in its theoretical size of ~12 kDa in mice and if it is affected by exercise. Male mice were randomly assigned to a sedentary control group (CO), a grou ...[more]

PMID: 24644429

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Project description:BackgroundCharcot-Marie-Tooth (CMT) indicates a group of inherited polyneuropathies whose clinical phenotypes primarily include progressive distal weakness and muscle atrophy. Compelling evidence showed that the exercise-mimetic myokine irisin protects against muscle wasting in an autocrine manner, thus possibly preventing the onset of musculoskeletal atrophy. Therefore, we sought to determine if irisin serum levels correlate with biochemical and muscle parameters in a cohort of CMT patients.MethodsThis cohort study included individuals (N=20) diagnosed with CMT disease. Irisin and biochemical markers were quantified in sera. Skeletal muscle mass (SMM) was evaluated by bioelectric impedance analysis, muscle strength by handgrip, and muscle quality was derived from muscle strength and muscle mass ratio.ResultsCMT patients (m/f, 12/8) had lower irisin levels than age and sex matched healthy subjects (N=20) (6.51 ± 2.26 vs 9.34 ± 3.23 μg/ml; p=0.003). SMM in CMT patients was always lower compared to SMM reference values reported in healthy Caucasian population matched for age and sex. Almost the totality of CMT patients (19/20) showed low muscle quality and therefore patients were evaluated on the basis of muscle strength. Irisin was lower in presence of pathological compared to normal muscle strength (5.56 ± 1.26 vs 7.67 ± 2.72 μg/ml; p=0.03), and directly correlated with the marker of bone formation P1PN (r= 0.669; 95%CI 0.295 to 0.865; p=0.002), but inversely correlated with Vitamin D (r=-0.526; 95%CI -0,791 to -0,095; p=0.017). Surprisingly, in women, irisin levels were higher than in men (7.31 ± 2.53 vs 5.31 ± 1.02 μg/ml, p=0.05), and correlated with both muscle strength (r=0.759; 95%CI 0.329 to 0.929; p=0.004) and muscle quality (r=0.797; 95%CI 0.337 to 0.950; p=0.006).ConclusionOur data demonstrate lower irisin levels in CMT patients compared to healthy subjects. Moreover, among patients, we observed, significantly higher irisin levels in women than in men, despite the higher SMM in the latter. Future studies are necessary to establish whether, in this clinical contest, irisin could represent a marker of the loss of muscle mass and strength and/or bone loss.

Project description:Mice overexpressing NAMPT in skeletal muscle (NamptTg mice) develop higher exercise endurance and maximal aerobic capacity (VO2max) following voluntary exercise training compared to wild-type (WT) mice. Here, we aimed to investigate the mechanisms underlying by determining skeletal muscle mitochondrial respiratory capacity in NamptTg and WT mice. Body weight and body composition, tissue weight (gastrocnemius, quadriceps, soleus, heart, liver, and epididymal white adipose tissue), skeletal muscle and liver glycogen content, VO2max, skeletal muscle mitochondrial respiratory capacity (measured by high-resolution respirometry), skeletal muscle gene expression (measured by microarray and qPCR), and skeletal muscle protein content (measured by Western blot) were determined following 6 weeks of voluntary exercise training (access to running wheel) in 13-week-old male NamptTg (exercised NamptTg) mice and WT (exercised WT) mice. Daily running distance and running time during the voluntary exercise training protocol were recorded. Daily running distance (p = 0.51) and running time (p = 0.85) were not significantly different between exercised NamptTg mice and exercised WT mice. VO2max was higher in exercised NamptTg mice compared to exercised WT mice (p = 0.02). Body weight (p = 0.92), fat mass (p = 0.49), lean mass (p = 0.91), tissue weight (all p > 0.05), and skeletal muscle (p = 0.72) and liver (p = 0.94) glycogen content were not significantly different between exercised NamptTg mice and exercised WT mice. Complex I oxidative phosphorylation (OXPHOS) respiratory capacity supported by fatty acid substrates (p < 0.01), maximal (complex I+II) OXPHOS respiratory capacity supported by glycolytic (p = 0.02) and fatty acid (p < 0.01) substrates, and maximal uncoupled respiratory capacity supported by fatty acid substrates (p < 0.01) was higher in exercised NamptTg mice compared to exercised WT mice. Transcriptomic analyses revealed differential expression for genes involved in oxidative metabolism in exercised NamptTg mice compared to exercised WT mice, specifically, enrichment for the gene set related to the SIRT3-mediated signaling pathway. SIRT3 protein content correlated with NAMPT protein content (r = 0.61, p = 0.04). In conclusion, NamptTg mice develop higher exercise capacity following voluntary exercise training compared to WT mice, which is paralleled by higher mitochondrial respiratory capacity in skeletal muscle. The changes in SIRT3 targets suggest that these effects are due to remodeling of mitochondrial function.

Project description:MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNA species involved in post-transcriptional gene regulation. In vitro studies have identified a small number of skeletal muscle-specific miRNAs which play a crucial role in myoblast proliferation and differentiation. In skeletal muscle, an acute bout of endurance exercise results in the up-regulation of transcriptional networks that regulate mitochondrial biogenesis, glucose and fatty acid metabolism, and skeletal muscle remodelling. The purpose of this study was to assess the expressional profile of targeted miRNA species following an acute bout of endurance exercise and to determine relationships with previously established endurance exercise responsive transcriptional networks. C57Bl/6J wild-type male mice (N = 7/group) were randomly assigned to either sedentary or forced-endurance exercise (treadmill run @ 15 m/min for 90 min) group. The endurance exercise group was sacrificed three hours following a single bout of exercise. The expression of miR- 181, 1, 133, 23, and 107, all of which have been predicted to regulate transcription factors and co-activators involved in the adaptive response to exercise, was measured in quadriceps femoris muscle. Endurance exercise significantly increased the expression of miR-181, miR-1, and miR-107 by 37%, 40%, and 56%, respectively, and reduced miR-23 expression by 84% (P<or=0.05 for all), with no change in miR-133. Importantly, decreased expression of miRNA-23, a putative negative regulator of PGC-1alpha was consistent with increased expression of PGC-1alpha mRNA and protein along with several downstream targets of PGC-1alpha including ALAS, CS, and cytochrome c mRNA. PDK4 protein content remains unaltered despite an increase in its putative negative regulator, miR-107, and PDK4 mRNA expression. mRNA expression of miRNA processing machinery (Drosha, Dicer, and DGCR8) remained unchanged. We conclude that miRNA-mediated post-transcriptional regulation is potentially involved in the complex regulatory networks that govern skeletal muscle adaptation to endurance exercise in C57Bl/6J male mice.

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Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise.

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Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise.

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