Irisin Release Research Articles

An Examination of Exercise Intensity and its Impact on the Acute Release of Irisin Across Obesity Status: A Randomized Controlled Crossover Trial.

Limited data exist regarding the impact of exercise intensity on irisin release and its association with insulin sensitivity in individuals of differing obesity status. The objective of this study was to investigate the impact of exercise intensity on the acute release of irisin in healthy weight individuals and individuals with obesity, and whether irisin release during acute exercise was associated with greater insulin sensitivity across obesity status. A randomized controlled crossover study was conducted on 26 non-obese (NOB) (BMI: 22.2±1.5 kg/m2) and 26 OB (BMI: 33.9±6.5 kg/m2) adults who performed an acute bout of moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), and rest. Irisin was quantified via ELISA and western blotting, and insulin sensitivity (Si) was estimated using the Matsuda index. OB displayed a significantly lower level of circulating irisin and protein expression compared to NOB (p<0.01). Insulin sensitivity was positively correlated with irisin release during MICT and HIIT in NOB (all p<0.05), but not in OB. Regarding irisin expression, NOB with high-Si had a 2.03-fold (p<0.05) increase during HIIT, while OB with high-Si had only a 1.54-fold increase (p<0.05). These results suggest that irisin is released differently according to obesity status and varying exercise intensities. OB individuals have a blunted irisin response to acute exercise and lower baseline irisin concentrations compared to NOB individuals. Although exercise stimulates irisin release in NOB individuals, only a greater exercise intensity stimulates irisin release in OB individuals. These findings are clinically relevant, as irisin is associated with greater insulin sensitivity.

The time course of irisin release after an acute exercise: relevant implications for health and future experimental designs.

This study aimed to analyze the acute impact of exercise on serum irisin levels in 22 young (YA, 24.6 ± 3.5 yrs) and in 12 middle-aged male adults (MA, 54.6 ± 5.7 yrs) 15 min and 24 h after an incremental cycling exercise test to exhaustion. ELISA assay was used for serum irisin detection. Circulating irisin increased significantly from baseline (9.0 ± 2.0 ng/ml) to 15 min post-exercise (10.2 ± 2.0 ng/ml, P < 0.001), but the greatest increment was detected after 24 h (13.5 ± 2.5 ng/ml, P < 0.001) reaching more than 50% of the basal release. Levels were significantly higher in YA (9.7 ± 1.7 to 11.1 ± 1.8 to 14.5 ± 2.2 ng/ml) than MA (7.6 ± 1.6 to 8.7 ± 1.5 to 11.8± 2.2 ng/ml) for all measured time-points (P < 0.05). Nevertheless, MA showed a comparable increase in serum irisin levels when compared to YA. These findings highlight the importance of acute physical exercise as a countermeasure against age-related deterioration of skeletal muscle mass and function in both YA and MA.

Bone formation by Irisin-Poly vinyl alchol modified bioglass ceramic beads in the rabbit model

In the aging society, slow bone regeneration poses a serious hindrance to the quality of life. To deal with this problem, in this study, we have combined irisin with the bioglass regular beads to enhance the bone regeneration process. For this purpose, highly porous bioglass was obtained as spherical beads by using sodium alginate. The bioglass was evaluated by various analytical techniques such as SEM, EDS, XRD, and pore size distribution. The results depicted that porous bioglass was prepared correctly and SEM analysis showed a highly porous bioglass was formulated. On this bioglass, irisin was loaded with the assistance of polyvinyl alcohol (PVA) in three concentrations (50 ng/ml, 100 ng/ml, and 150 ng/ml per 1 g of bioglass). SEM analysis showed that pores are covered with PVA. The irisin release profile showed a sustained release over the time period of 7 days. In vitro, biocompatibility evaluation by the MC3T3E1 cells showed that prepared bioglass and irisin loaded bioglass (BGI50, BGI100, and BG150) are highly biocompatible. Alizarin Red staining analysis showed that after 2 weeks BGI50 samples showed highest calcium nodule formation. In vivo in the rabbit femur model was conducted for 1 and 2 months. BGI150 samples showed highest BV/TV ratio of 37.1 after 2 months. The histological data showed new bone formation surrounding the beads and with beads loaded with irisin. Immunohistochemistry using markers OPN, RUNX, COL, and ALP supported the osteogenic properties of the irisin-loaded bioglass beads. The results indicated that irisin-loaded bioglass displayed remarkable bone regeneration.Graphical

The Acute and Chronic Effect of Endurance Versus Resistance Exercise on Circulating Irisin: A Systematic Review and Meta-Analysis

Abstract Background Exercise-induced release of irisin is associated with various improved health outcomes. However, the most effective exercise mode(s) to stimulate irisin release remain unclear. In this systematic review, we separately examine potential differences in (i) resting irisin concentrations (chronic change) after resistance (RT) and endurance training (ET) and (ii) the concentrations of irisin after a single bout (acute change) of resistance (RE) and endurance exercise (EE). Methods Searching was completed February 2022 in PubMed, CINAHL, Web of Science, Cochrane Library, SCOPUS, and SportDiscus. Studies were included by consensus of 2 reviewers, if they were randomized controlled trials (RCTs) or comparison studies with adults over 18 years and compared chronic change after RT and ET for any intervention duration or acute change after RE and EE. Risk of bias and quality of findings were independently assessed using PEDRo and GRADE, respectively. Irisin post means and standard deviations were extracted to calculate standardized mean differences (SMDs) and 95% confidence intervals using a random effect model. Results Of 174 studies screened, 8 chronic and 4 acute studies were included in the analysis, comprising a total of 332 participants. No difference between RT or ET for chronic irisin response was found (P = 0.380, SMD = 0.17, n = 248); however, there tended to be greater acute increases in circulating irisin after RE than EE (P &amp;lt; 0.001, SMD = 0.93, n = 56). Conclusions A greater effect of RE on irisin concentrations than EE was found in acute studies. Future research requires larger sample sizes and matched intensities.

Effect of High-Intensity Resistance Training Versus Endurance Training on Irisin and Adipomyokine Levels in Healthy Individuals: An 8-Week Interventional Study.

Background: Irisin and adipomyokine are proteins secreted by the body during exercise and exhibit potential therapeutic effects for chronic disorders. Gaining insights into how high-intensity resistance training and endurance training influence irisin and adipomyokine secretion could shed light on optimizing exercise regimens for potential therapeutic applications. Such knowledge could pave the way for personalized exercise prescriptions and contribute to the development of novel treatments for chronic conditions, enhancing overall health and well-being. Objectives: To investigate the effects of high-intensity resistance training (HIRT) and endurance training on irisin and adipomyokine levels in healthy individuals. Methods: An 8-week interventional comparative study was conducted at Nimra Institute of Medical Sciences, Andhra Pradesh, India. One hundred healthy male individuals aged 21 to 35 were divided into two groups: HIRT and endurance. The HIRT group performed high-intensity resistance training, while the endurance group performed endurance training. Ethical approval was obtained, and baseline and post-intervention values of the participants were recorded and analyzed using SPSS software. Results: After 8 weeks, irisin levels were significantly elevated in the HIRT group (167.39±11.27) compared to the endurance group (155.39±11.28). A positive correlation was observed between skeletal muscle and irisin levels in both the HIRT group (χ2-16.38; p=0.04) and the endurance group (χ2-18.36; p=0.01). Additionally, TNF-α (HIRT: 81.47±4.02 and Endurance: 61.19±4.00) and interleukin-6 (IL-6) (HIRT: 46.84±4.46 and Endurance: 36.15±3.89) levels significantly increased in the HIRT group. However, there was no significant change in leptin levels in either group (HIRT: 3.75±0.58 0.58 and 4.15±0.58). Conclusion: The findings of this study indicate that HIRTis more effective in increasing irisin levels compared to endurance training. However, the notable elevation of IL-6and TNF-α in the HIRT group raises concerns about potential chronic inflammation. To optimize outcomes, a combined approach, coupling HIRT and endurance training, may be beneficial. Additionally, the results emphasize the significance of skeletal muscle as a primary source of irisin secretion, implying that increased muscle contraction contributes to higher irisin release even in healthy individuals. These insights can guide exercise prescriptions and potentially enhance therapeutic strategies for chronic disorders.

Neuroplasticity to autophagy cross-talk in a therapeutic effect of physical exercises and irisin in ADHD.

Adaptive neuroplasticity is a pivotal mechanism for healthy brain development and maintenance, as well as its restoration in disease- and age-associated decline. Management of mental disorders such as attention deficit hyperactivity disorder (ADHD) needs interventions stimulating adaptive neuroplasticity, beyond conventional psychopharmacological treatments. Physical exercises are proposed for the management of ADHD, and also depression and aging because of evoked brain neuroplasticity. Recent progress in understanding the mechanisms of muscle-brain cross-talk pinpoints the role of the myokine irisin in the mediation of pro-cognitive and antidepressant activity of physical exercises. In this review, we discuss how irisin, which is released in the periphery as well as derived from brain cells, may interact with the mechanisms of cellular autophagy to provide protein recycling and regulation of brain-derived neurotrophic factor (BDNF) signaling via glia-mediated control of BDNF maturation, and, therefore, support neuroplasticity. We propose that the neuroplasticity associated with physical exercises is mediated in part by irisin-triggered autophagy. Since the recent findings give objectives to consider autophagy-stimulating intervention as a prerequisite for successful therapy of psychiatric disorders, irisin appears as a prototypic molecule that can activate autophagy with therapeutic goals.

241-OR: Effects of Antidiabetes Therapies on Irisin Levels in Type 2 Diabetes Patients

Irisin is a hormone secreted by skeletal muscle following physical activity or excess of saturated fatty acids, able to promote energy expenditure and improve metabolic homeostasis. Serum irisin levels are reduced in type 2 diabetes (T2D), while exogenous irisin administration improves glycemic control in diabetic mice. We have previously demonstrated that irisin promotes beta-cell viability and insulin secretory function. This study investigated serum irisin levels in T2D patients according to their antidiabetes treatment. 127 T2D patients were enrolled and stratified by antidiabetes therapy: diet only (17); metformin only (met, 37); met plus sulfonylureas (5); met plus pioglitazone (7); met plus GLP-1 receptor agonists (GLP-1RAs, 31); met plus DPP-4 inhibitors (DPP-4i, 15); and met plus SGLT2 inhibitors (SGLT2i, 15). The control group included 36 sex-, and BMI-matched subjects without diabetes. T2D patients showed lower irisin levels than controls (21.5 [10.1-50.8] vs. 29.1 [14.1-43.5] ng/mL, P&amp;lt;0.01). Serum irisin levels were positively associated with diabetes duration (r=0.214, P&amp;lt;0.05) and negatively associated with total (r=-0.196, P&amp;lt;0.05) and LDL cholesterol (r=-0.214, P&amp;lt;0.05). Patients treated with met plus GLP-1RAs or DPP-4i showed increased serum irisin levels (28.1 [12.4-50.8] and 25.8 [13.2-37.8] ng/mL, respectively) compared to patients treated with diet or met (19.8 [13.5-40.5] and 16.9 [10.7-28.8] ng/ml, respectively; P&amp;lt;0.05), or with other diabetes therapies. Interestingly, in vitro treatment of human skeletal muscle cells with 10 nM exendin-4 resulted in enhanced irisin release in the culture medium compared to control. In conclusion, in T2D GLP-1-based therapies significantly increase serum irisin to levels comparable to those of nondiabetic subjects, possibly through GLP-1 receptor-mediated stimulation of irisin release by skeletal muscle cells. Irisin may thus represent a new factor in the mechanism of action of GLP-1-based therapies. Disclosure A. Natalicchio: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Sanofi. S. Perrini: None. L. Laviola: Advisory Panel; Self; A. Menarini Diagnostics, Abbott, AstraZeneca, Lilly Diabetes, Novo Nordisk Inc., Roche Diabetes Care, Sanofi-Aventis, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Medtronic. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. N. Marrano: None. G. Biondi: None. A. Montedoro: None. G. Le grazie: None. L. Di gioia: None. F. Guarini: None. A. Borrelli: None. A. Cignarelli: None. Funding European Union–European Social Fund; PON R&amp;I (2014-2020); AIM (1810057)

Exercise in the cold causes greater irisin release but may not be enough for adropin.

When irisin and adropin were discovered, it was popularly hoped that they would become therapies for metabolic disorders that threaten global health. However, contradictory results have been reported in the subsequent period. Irisin, induced by exercise or cold exposure, is believed to be a myokine that causes the browning of adipose tissue thus increasing energy expenditure. Adropin is thought to be beneficial for health by regulating blood flow, capillary density, and playing an active role in glucose and insulin homeostasis. However, there were no experimental studies investigating the simultaneous effect of exercise and cold exposure in humans. The purpose of this study was to investigate irisin and adropin responses in young healthy individuals performing aerobic exercise in different environmental temperatures. Twenty-seven young, healthy individuals participated in this study. Participants performed 40 min of aerobic running exercise in environmental temperatures of 0°C, 12°C, and 24°C. Venous blood samples were taken pre- and post-exercise. Irisin and adropin levels were analyzed using an enzyme-linked immunosorbent assay. The principal findings showed that while serum irisin concentrations significantly increased after aerobic exercise was performed at an environmental temperature of 0°C, there was no significant difference between pre- and post-exercise recordings for physical activity performed at 12°C and 24°C. Adropin concentrations, however, remained unchanged between pre- and post-exercise at 0°C, 12°C, and 24°C. Interestingly, the exercise at 0°C caused an increase in adropin (12.5%), but this amount was not enough to be a statistically significant result. The findings of this study suggest that aerobic exercise in a cold environment causes greater irisin release. However, the combined effect of exercise and cold exposure may not be enough to statistically increase adropin level.

Concentrations of Circulating Irisin and Myostatin in Race and Endurace Purebred Arabian Horses—Preliminary Study

Simple SummaryIrisin and myostatin are regulatory proteins produced by muscle cells. The aim of the study was to evaluate the effect of exercise on plasma irisin and myostatin concentrations in horses in different types of training (speed versus endurance). To find out, we tested 20 Arabian horses, submitted to the two different equestrian disciplines, and consequently different training regimes. The first group of horses realized a short-term, high-speed bout of exercise whereas the second group of horses were submitted to long-lasting, endurance effort. The obtained results showed that the single bout of exercise induced an increase in plasma myostatin concentration. Plasma irisin level decreased during the race season in racehorses. This means that irisin and myostatin may play a regulatory role in the maintenance of the energy balance processes. Skeletal muscle is considered to be the largest endocrine organ determining the maintenance of energy homeostasis. Adaptive changes in skeletal muscles in response to physical exercise influence the production as well as secretion of myokines, which are bioactive factors that play a crucial role in energy expenditure processes. The aim of the study was to investigate the impact of two different types of exercise on the circulating level of two of these, myostatin and irisin, in trained horses. Twenty purebred Arabian horses were involved in the study: 10 three-year-old horses trained on the racetrack and 10 endurance horses aged 7.4 ± 1.9 years. The horses from both groups were regularly trained throughout the entire season, during which they also participated in Polish National competitions. To assess the influence of the training sessions on plasma myostatin and irisin concentrations, blood samples taken at rest and 30 min after the end of exercise were analyzed. In the studied horses, the single bout of exercise did not influence plasma irisin but induced an increase in plasma myostatin concentration. In racehorses, plasma irisin concentration decreased with the length of the training season. Plasma myostatin was higher in endurance horses than in three-year-old racehorses. Lack of exercise-induced fluctuation in circulating irisin in studied horses suggests that myostatin released in response to exercise provides a negative feedback signal to irisin release.

Autonomic function may not modulate irisin release in healthy adults: findings from a randomized cross-over study.

Autonomic nervous system, especially the sympathetic nervous system, may stimulate the expression of peroxisome proliferator-activated receptor γ coactivator-1α, which regulates irisin. This study aimed to explore whether there was any association between autonomic function as assessed by heart rate related indices and irisin release following acute exercise. Seventeen healthy adults were asked to perform an incremental exhaustive cycling as well as an incremental exhaustive running separately on different days. Heart rate was monitored, and blood samples were collected before, immediately, 10-, and 60-minutes post-exercise. Serum irisin was measured using ELISA kit. Markers for autonomic function, such as heart rate at rest, peak, or recovery, heart rate reserve, heart rate recovery, and chronotropic index, were comparable between cycling and running (all P > 0.10). Irisin was increased immediately following both exercise. No significant association was observed between heart rate at rest, peak, or recovery and irisin level at the corresponding time-point, as well as between heart rate reserve, heart rate recovery, or chronotropic index and exercise induced irisin release, with or without controlling for age, body mass index, and glucose (all P > 0.10). Autonomic function might not be associated with irisin release in healthy adults. Arch Endocrinol Metab. 2020;64(3):201-4.

Irisin: A Hope in Understanding and Managing Obesity and Metabolic Syndrome

White adipose tissue (WAT) is an endocrine organ highly integrated in homeostasis and capable of establishing ways of communicating and influencing multiple metabolic processes. Brown adipose tissue promotes energy expenditure by incorporating the uncoupling protein 1 (UCP1), also known as thermogenin, which decouples cellular respiration and heat production, in the mitochondrial membranes. Recent data suggest the presence of a thermogenic cell formation from white adipocytes (beige or brite cells) with a potential role in preventing obesity and metabolic syndrome. The formation of these cells is influenced by physical exertion that induces expression of PPARγ coactivator-1 (PGC1) and downstream membrane protein, fibronectin type III domain-containing protein 5 (FNDC5) in skeletal muscle. Irisin, a thermogenic adipomyokine produced by FNDC5 cleavage is involved in the browning of adipose tissue. While animal studies are congruent with regard to the relationship between physical exertion and irisin release, the results from human studies are less than clear. Therefore, this review focuses on recent advances in our understanding of muscle and adipose tissue thermogenesis. Further, it describes the molecular mechanisms by which irisin impacts exercise, glucose homeostasis and obesity. Finally, the review discusses current gaps and controversies related to irisin release, its mode of action and its future potential as a therapeutic tool in managing obesity and metabolic syndrome.

CHANGES IN IRISIN RELEASE IN RESPONSE TO PERIPHERAL KISSPEPTIN-10 ADMINISTRATION IN HEALTHY AND OBESE ADULT MEN.

Kisspeptin role in metabolism has been implicated recently. However, the nature of the signals that may connect body fat/muscle tissues with the central nervous system governing energy homeostasis remains to be elucidated. The present study was designed to investigate the effects of peripheral kisspeptin-10 administration on irisin release in human males. Kisspeptin-10 was administered to normal weight (n=8) and obese (n=8) men. Sequential blood sampling was performed for 30 minutes pre and 210 minutes post kisspeptin injection at 30 minutes interval. ELISA kit was used to detect plasma irisin levels. There is a significant (P<0.0001) effect of Kisspeptin-10 administration on irisin release in both normal weight and obese participants. Mean irisin levels (96.24 ± 1.351 ng/mL) at 210 minutes were significantly (P<0.0001) enhanced as compared to pre-kisspeptin (59.18 ± 4.815 ng/mL) in normal weight subjects. In obese subjects mean irisin levels (75.76 ± 4.06 ng/mL) were significantly (P<0.0001) elevated at 180 minutes post-kisspeptin when compared with pre-kisspeptin irisin levels (41.28 ± 2.89 ng/mL). Our findings suggest that kisspeptin may have a novel therapeutic potential to induce irisin release in humans which may have anti-obesity effects.

Acute exercise-induced irisin release in healthy adults: Associations with training status and exercise mode

There is a growing interest in exploring irisin response to acute exercise; however, the associations of acute exercise-induced irisin release with training status and exercise mode are not fully understood. This study was primarily designed to evaluate these associations. Sixteen healthy adults (8 trained versus 8 untrained) underwent a bout of cycling at 80% of maximal oxygen uptake (VO2max) for 50 min, with blood drawn pre-, 10-, and 180-min post-exercise. Another 17 healthy adults performed 2 bouts of graded exercise (cycling and running) until exhaustion on separate days using a randomized cross-over design, with blood taken pre-, 0-, 10-, and 60-min post-exercise. Circulating irisin, creatine kinase (CK), aspartate aminotransferase (AST), and myoglobin (Mb) were measured, and their respective areas under the curves (AUCs) were calculated. Irisin increased 10-min after 50 min of cycling at 80% of VO2max, while its changes from baseline to post-exercise and the amount of exercise-induced irisin release (presented as AUC) were comparable between trained and untrained adults (all P > .05). Irisin remained elevated 10-min post-exhausting running but decreased towards baseline 10-min post-exhausting cycling. Exhausting running induced an increase in irisin release for the whole course of exercise and recovery periods, but cycling did not. Acute exercise-induced irisin changes seemed not related to changes of CK, aspartate AST, and Mb in general. In conclusion, acute exercise-induced irisin release is not associated with training status but might be affected by training mode. Future studies are required to investigate which exercise mode might be most efficient in altering irisin.

Effects of running a marathon on irisin concentration in men aged over 50

Our aim was to verify whether running a marathon is associated with changes in irisin concentration in healthy, endurance-trained men. In an observational study, we assessed baseline biochemical and fitness parameters of 28 middle-aged runners (mean ± SD age, BMI, VO2max: 58 ± 8 years; 24.5 ± 3 kg/m2; 51.1 ± 1.7 ml/kg/min). We evaluated irisin before, immediately after, and 7 days after the marathon. Irisin concentration decreased from a baseline value of 639 ± 427 to 461 ± 255 ng/ml immediately after the marathon (p < 0.05). After 7 days, it was still significantly lower than before the race, at 432 ± 146 ng/ml (p < 0.05). We found no correlations between irisin concentration and the training history of the studied subjects. We conclude that a long-distance run may have a negative impact on irisin release in men. This effect was not correlated with the training history of runners.

Central irisin administration affords antidepressant-like effect and modulates neuroplasticity-related genes in the hippocampus and prefrontal cortex of mice

Evidence has indicated that the practice of physical exercise has antidepressant effects that might be associated with irisin release and BDNF signaling. In this study we investigated the effects of the central administration of irisin or BDNF in predictive tests of antidepressant properties paralleled with the gene expression of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF) in the hippocampus and prefrontal cortex of mice. Irisin (0.5–1 ng/mouse, i.c.v.) reduced the immobility time in the tail suspension test (TST) and forced swim test (FST), without altering locomotion in the open field test (OFT). Irisin reduced the immobility time in the TST up to 6 h after its administration. Irisin administration (6 h) increased PGC-1α mRNA in the hippocampus and prefrontal cortex and reduced (1 h) PGC-1α mRNA in the prefrontal cortex. FNDC5 and BDNF mRNA expression was decreased (1 h) in both structures and remained reduced up to 6 h in the prefrontal cortex. Moreover, BDNF administered at 0.25 μg/mouse, i.c.v. (1 and 6 h before the test) reduced the immobility time in the TST. BDNF administration reduced PGC-1α mRNA in the hippocampus (6 h) and prefrontal cortex (1 and 6 h). It also increased FNDC5 mRNA expression in the hippocampus (1 and 6 h), but reduced the expression of this gene and also BDNF mRNA in the prefrontal cortex (1 and 6 h). None of the treatments altered BDNF protein levels in both structures. In conclusion, irisin presents a behavioral antidepressant profile similar to BDNF, an effect associated with the modulation of gene expression of PGC-1α, FNDC5 and BDNF, reinforcing the pivotal role of these genes in mood regulation.

Is irisin the new player in exercise-induced adaptations or not? A 2017 update.

Irisin is produced by a proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5) and has emerged as a potential mediator of exercise-induced energy metabolism. The purpose of this study was to review the results of studies that investigated irisin responses to acute and chronic exercise and provide an update. A comprehensive search in the databases of MEDLINE was performed (74 exercise studies). The focus of the analysis was on data concerning FNDC5 mRNA expression in skeletal muscle and circulating irisin concentration relatively to exercise mode, intensity, frequency and duration and the characteristics of the sample used. Circulating irisin levels may either not relate to FNDC5 transcription or expression of the later precedes irisin rise in the blood. Acute speed/strength and endurance exercise protocols represent potent stimuli for irisin release if they are characterized by adequate intensity and/or duration. There are no reports regarding irisin responses to field sport activities. Although animal studies suggest that irisin may also respond to systematic exercise training, the majority of human studies has produced contradictory results. Certain methodological issues need to be considered here such as the analytical assays used to measure irisin concentration in the circulation. Results may also be affected by subjects' age, conditioning status and exercise intensity. The role of irisin as a moderator of energy metabolism during exercise remains to be seen.

The Myokine Irisin Is Released in Response to Saturated Fatty Acids and Promotes Pancreatic β-Cell Survival and Insulin Secretion.

This study explored the role of irisin as a new pancreatic β-cell secretagogue and survival factor and its potential role in the communication between skeletal muscle and pancreatic β-cells under lipotoxic conditions. Recombinant irisin stimulated insulin biosynthesis and glucose-stimulated insulin secretion (GSIS) in a PKA-dependent manner and prevented saturated fatty acid-induced apoptosis in human and rat pancreatic β-cells, as well as in human and murine pancreatic islets, via AKT/BCL2 signaling. Treatment of myotubes with 0.5 mmol/L palmitate for 4 h, but not with oleate, promoted an increase in irisin release in the culture medium. Moreover, increased serum levels of irisin were observed in mice fed with a high-fat diet. Mouse serum rich in irisin and the conditioned medium from myotubes exposed to palmitate for 4 h significantly reduced apoptosis of murine pancreatic islets and insulin-secreting INS-1E cells, respectively, and this was abrogated in the presence of an irisin-neutralizing antibody. Finally, in vivo administration of irisin improved GSIS and increased β-cell proliferation. In conclusion, irisin can promote β-cell survival and enhance GSIS and may thus participate in the communication between skeletal muscle and β-cells under conditions of excess saturated fatty acids.

Circulating Irisin is Increased in Type 2 Diabetes Mellitus and Correlates with Fasting Glucose Levels

Abstract Background/aims Irisin is a hormone expressed in muscle, which is an exercise-induced myokine triggering browning of white adipose tissue and increases metabolic genes expression. Methods We investigated the irisin levels in 39 type 2 diabetes mellitus patients (T2D) compared to 39 control individuals. Results Irisin plasma levels were higher in T2D patients when compared with the control group ( p p p =0.011, respectively). Obese T2D individuals showed higher irisin levels when compared with non-obese control ( p =0.003), but no difference was observed when compared with obese controls ( p >0.05). A positive correlation was observed between irisin and fasting glucose levels in the T2D group ( r =0.341, p =0.033). No difference regarding irisin levels was found when T2D individuals who practice physical activity and sedentary individuals were compared ( p =0.632). Conclusion This result indicates that T2D is associated with an irisin release in order to compensate the insulin resistance observed in the skeletal muscle on diabetes, and that the poor glycaemic control contributes for enhancement of this state.

Irisin Controls Growth, Intracellular Ca2+ Signals, and Mitochondrial Thermogenesis in Cardiomyoblasts.

Exercise offers short-term and long-term health benefits, including an increased metabolic rate and energy expenditure in myocardium. The newly-discovered exercise-induced myokine, irisin, stimulates conversion of white into brown adipocytes as well as increased mitochondrial biogenesis and energy expenditure. Remarkably, irisin is highly expressed in myocardium, but its physiological effects in the heart are unknown. The objective of this work is to investigate irisin’s potential multifaceted effects on cardiomyoblasts and myocardium. For this purpose, H9C2 cells were treated with recombinant irisin produced in yeast cells (r-irisin) and in HEK293 cells (hr-irisin) for examining its effects on cell proliferation by MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and on gene transcription profiles by qRT-PCR. R-irisin and hr-irisin both inhibited cell proliferation and activated genes related to cardiomyocyte metabolic function and differentiation, including myocardin, follistatin, smooth muscle actin, and nuclear respiratory factor-1. Signal transduction pathways affected by r-irisin in H9C2 cells and C57BL/6 mice were examined by detecting phosphorylation of PI3K-AKT, p38, ERK or STAT3. We also measured intracellular Ca2+ signaling and mitochondrial thermogenesis and energy expenditure in r-irisin-treated H9C2 cells. The results showed that r-irisin, in a certain concentration rage, could activate PI3K-AKT and intracellular Ca2+ signaling and increase cellular oxygen consumption in H9C2 cells. Our study also suggests the existence of irisin-specific receptor on the membrane of H9C2 cells. In conclusion, irisin in a certain concentration rage increased myocardial cell metabolism, inhibited cell proliferation and promoted cell differentiation. These effects might be mediated through PI3K-AKT and Ca2+ signaling, which are known to activate expression of exercise-related genes such as follistatin and myocardin. This work supports the value of exercise, which promotes irisin release.

Circulating irisin levels and muscle FNDC5 mRNA expression are independent of IL-15 levels in mice.

Interleukin-15 (IL-15) and irisin are exercise-induced myokines that exert favorable effects on energy expenditure and metabolism. IL-15 can induce PGC-1α expression, which in turn induces expression of irisin and its precursor, FNDC5. Therefore, the present study tested the hypothesis that increases in circulating irisin levels and muscle FNDC5 mRNA expression are dependent on IL-15. Circulating irisin levels and gastrocnemius muscle FNDC5 mRNA expression were examined following acute exercise in control and IL-15-deleted (IL-15 KO) mice, following injection of IL-15 into IL-15 KO mice, and in transgenic mice with elevated circulating IL-15 levels (IL-15 Tg mice). Circulating IL-15 levels and muscle PGC-1α and PPARδ mRNA expressions were determined as positive controls. No effect of IL-15 deletion on post-exercise serum irisin levels or muscle FNDC5 mRNA expression was detected. While serum IL-15 levels and muscle PGC-1α expression were elevated post-exercise in control mice, both serum irisin levels and muscle FNDC5 expression decreased shortly after exercise in both control and IL-15 KO mice. A single injection of recombinant IL-15 into IL-15 KO mice that significantly increased muscle PPARδ and PGC-1α mRNA expressions had no effect on circulating irisin release, but modestly induced muscle FNDC5 expression. Additionally, serum irisin and gastrocnemius muscle FNDC5 expression in IL-15 Tg mice were similar to those of control mice. Muscle FNDC5 mRNA expression and irisin release are not IL-15-dependent in mice.