Irisin Secretion Research Articles

Effects of Irisin Secretion on the Development of Kidney Injury in a Mouse Model of Uremic Sarcopenia

Effects of Irisin Secretion on the Development of Kidney Injury in a Mouse Model of Uremic Sarcopenia

Irisin Protects Musculoskeletal Homeostasis via a Mitochondrial Quality Control Mechanism.

Irisin, a myokine derived from fibronectin type III domain-containing 5 (FNDC5), is increasingly recognized for its protective role in musculoskeletal health through the modulation of mitochondrial quality control. This review synthesizes the current understanding of irisin's impact on mitochondrial biogenesis, dynamics, and autophagy in skeletal muscle, elucidating its capacity to bolster muscle strength, endurance, and resilience against oxidative-stress-induced muscle atrophy. The multifunctional nature of irisin extends to bone metabolism, where it promotes osteoblast proliferation and differentiation, offering a potential intervention for osteoporosis and other musculoskeletal disorders. Mitochondrial quality control is vital for cellular metabolism, particularly in energy-demanding tissues. Irisin's influence on this process is highlighted, suggesting its integral role in maintaining cellular homeostasis. The review also touches upon the regulatory mechanisms of irisin secretion, predominantly induced by exercise, and its systemic effects as an endocrine factor. While the therapeutic potential of irisin is promising, the need for standardized measurement techniques and further elucidation of its mechanisms in humans is acknowledged. The collective findings underscore the burgeoning interest in irisin as a keystone in musculoskeletal health and a candidate for future therapeutic strategies.

Swimming alleviates myocardial fibrosis of type II diabetic rats through activating miR-34a-mediated SIRT1/PGC-1α/FNDC5 signal pathway.

Myocardial fibrosis can trigger heart failure in diabetic cardiomyopathy (DCM), and irisin, an exercise-induced myokine, may have a beneficial effect on cardiac function. However, the specific molecular mechanism between exercise and irisin in the diabetic heart remains not fully explored. This study aimed to investigate how miR-34a mediates exercise-induced irisin to ameliorate myocardial fibrosis and its underlying mechanisms. Type 2 diabetes mellitus (T2DM) with DCM was induced in adult male rats with high-fat diet and streptozotocin injection. The DCM rats were subjected to swimming (60 min/d) and recombinant irisin (r-irisin, 500 μg/kg/d) interventions for 8 weeks, respectively. Cardiac function, cardiomyocyte structure, myocardial fibrosis and its correlated gene and protein expression were analyzed. Swimming intervention alleviated insulin resistance, myocardial fibrosis, and myocardial hypertrophy, and promoted blood glucose homeostasis in T2DM model rats. This improvement was associated with irisin upregulation and miR-34a downregulation in the myocardium, thus enhancing cardiac function. Similar efficacy was observed via intraperitoneal injection of exogenous recombinant irisin. Inhibition of miR-34a in vivo exhibited an anti-myocardial fibrotic effect by promoting irisin secretion through activating sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α)/fibronectin type III domain-containing protein 5 (FNDC5) signal pathway and downregulating myocardial fibrosis markers (collagen I, collagen III, and transforming growth factor-β1). Therefore, swimming-induced irisin has the potential therapeutic effect on diabetic myocardial fibrosis through activating the miR-34a-mediated SIRT1/PGC-1α/FNDC5 signal pathway.

Unlocking the potential of exercise: harnessing myokines to delay musculoskeletal aging and improve cognitive health.

This review aims to summarize the common physiological mechanisms associated with both mild cognitive impairment (MCI) and musculoskeletal aging while also examining the relevant literature on how exercise regulation influences the levels of shared myokines in these conditions. The literature search was conducted via databases such as PubMed (including MEDLINE), EMBASE, and the Cochrane Library of Systematic Reviews. The searches were limited to full-text articles published in English, with the most recent search conducted on 16 July 2024. The inclusion criteria for this review focused on the role of exercise and myokines in delaying musculoskeletal aging and enhancing cognitive health. The Newcastle‒Ottawa Scale (NOS) was utilized to assess the quality of nonrandomized studies, and only those studies with moderate to high quality scores, as per these criteria, were included in the final analysis. Data analysis was performed through narrative synthesis. The primary outcome of this study was the evaluation of myokine expression, which included IL-6, IGF-1, BDNF, CTSB, irisin, and LIF. A total of 16 studies involving 633 older adults met the inclusion criteria. The current exercise modalities utilized in these studies primarily consisted of resistance training and moderate-to high-intensity cardiovascular exercise. The types of interventions included treadmill training, elastic band training, aquatic training, and Nordic walking training. The results indicated that both cardiovascular exercise and resistance exercise could delay musculoskeletal aging and enhance the cognitive functions of the brain. Additionally, different types and intensities of exercise exhibited varying effects on myokine expression. Current evidence suggests that exercise mediates the secretion of specific myokines, including IL-6, IGF-1, BDNF, CTSB, irisin, and LIF, which establish self-regulatory circuits between the brain and muscle. This interaction enhances cognitive function in the brain and improves skeletal muscle function. Future research should focus on elucidating the exact mechanisms that govern the release of myokines, the correlation between the intensity of exercise and the secretion of these myokines, and the distinct processes by which myokines influence the interaction between muscle and the brain.

Effects of High-Intensity Intermittent Training on Metabolic Parameters and Irisin Levels in High-Fat-Fed Rats

Objective: To investigate the effects of high-intensity intermittent training (HIIT) on preventing significant weight gain and provide scientific theoretical support and practical guidance for reducing the occurrence of obesity. Methods: Twenty-four Sprague-Dawley rats were randomly divided into four groups: the control sedentary group (CS), the high-fat sedentary group (HS), the high-fat continuous exercise group (HE), and the high-fat intermittent exercise group (HI). The HE and HI groups underwent five days of continuous low-intensity exercise and eight weeks of high-intensity intermittent exercise. Weekly monitoring included measurements of food intake and body weight. An automatic biochemical analyzer was used to assess blood lipid and glucose levels, while ELISA kits measured serum insulin and irisin content. H&E staining was used to observe adipocyte size. Results: In the HS group, body weight, blood lipid levels, blood glucose levels, and adipocyte size significantly increased, while the QUICKI index decreased. In the HI group, body weight, blood lipid levels, blood glucose levels, and adipocyte size decreased, and the QUICKI index increased. The effects of high-intensity intermittent exercise were superior to those of continuous low-intensity exercise. In the HI group, serum irisin levels did not change significantly after exercise, while in the HE group, there was a slight upward trend in irisin levels. Conclusion: A high-fat diet induced abnormal metabolism in rats. HIIT effectively prevents metabolic abnormalities induced by a high-fat diet, and its effects are more pronounced than those of low-intensity exercise. HIIT stimulates the secretion of blood irisin, affecting secretion levels, and may represent a novel mechanism for maintaining metabolic homeostasis. This has important implications for controlling significant weight gain.

Irisin alleviates the pyroptosis of β cells in T2DM by inhibiting NLRP3 inflammasome through regulating miR-19b-3p/SOCS3/STAT3 axis mediated autophagy.

The purpose of this study was to analyze the mechanism by which irisin affects β-cell pyroptosis in type 2 diabetes mellitus (T2DM). The in vivo T2DM model was established by raised with high-fat diet and intraperitoneally injection of streptozocin. Min6 cells were divided into four groups: negative control (NC), high glucose (HG), HG + irisin, and HG + irisin+3-MA. The cell viability was determined by CCK-8 assay. Dual-luciferase gene reporter assay was conducted to confirm the binding between miR-19b-3p and SOCS3. The expression level of FNDC5 and GSDMD was visualized using the immunofluorescence assay. The protein level of FNDC5, Beclin1, LC3II/I, NLRP3, cleaved-caspase-1, GSDMD-N, STAT3, p-STAT3, and SOCS3 was determined by Western blotting. The secretion of irisin, lactate dehydrogenase (LDH), and insulin was checked by ELISA. In vivo results showed that pathological changes in islet tissues with declined number of β cells, elevated FBG value, decreased FIN and HOMA-β value, elevated autophagy-associated proteins expressions, and activated NLRP3 signaling in T2DM mice, which were dramatically reversed by FNDC5 overexpression. Furthermore, the declined level of miR-19b-3p and p-STAT3, as well as the upregulation of SOCS3, was greatly rescued by FNDC5 overexpression. The in vitro data confirmed the binding site between SOCS3 and miR-19b-3p. SOCS3 was downregulated and p-STAT3 was upregulated in miR-19b-3p mimic-treated Min6 cells. In HG-stimulated Min6 cells, the elevated cell viability, increased production of insulin, decreased release of LDH, and inactivated NLRP3 signaling induced by irisin were abolished by miR-19b-3p inhibitor and STAT3 inhibitor. The increased level of autophagy-related proteins and activated SOCS3/STAT3 axis induced by irisin in HG-stimulated Min6 cells were abolished by miR-19b-3p inhibitor. The inhibitory effect of irisin against NLRP3 signaling in HG-stimulated Min6 cells was abrogated by 3-MA. In conclusion, irisin alleviated the pyroptosis of β cells in T2DM by inhibiting NLRP3 signaling through miR-19b-3p/SOCS3/STAT3 axis mediated autophagy.

Can whole body vibration enhance chemotherapy?

In oncological patients, whole body vibration (WBV) can be used to reduce cancer therapy-related morbidities, including in the case of intensive/high-dose chemotherapy. Based on the fact that WBV has the unique effect among physical exercises of intensifying blood circulation in the splanchnic territory, the medical hypothesis can be formulated according to which this type of training performed immediately after or ideally during intravenous chemotherapy would enhance the effectiveness of drug therapy due to the increase in the rate of distribution. This effect, which can benefit especially patients with abdominal tumors, may also allow the reduction of doses, thus reducing the probability of the occurrence of adverse reactions. Testing the hypothesis is possible on experimental animals, but for the organization of the research protocol, it must be taken into account that mechanical vibrations can destroy tumor cells by their own action, by influencing mesenchymal stem cells or by stimulating the secretion of irisin. Research on experimental animals is also necessary to discern whether mechanical vibrations do not affect the treatment of tumors with stem cells or do not decrease anti-tumor immunity.

Hydrogen Sulfide and Irisin, Potential Allies in Ensuring Cardiovascular Health.

Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia-reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved.

Liraglutide promotes UCP1 expression and lipolysis of adipocytes by promoting the secretion of irisin from skeletal muscle cells

Although Liraglutide (Lira) increases serum irisin levels in type 2 diabetes mellitus (T2DM), it is unclear whether it induces expression of uncoupling protein 1 (UCP1) of adipocytes via promoting irisin secretion from skeletal muscle. Male T2DM rats were treated with 0.4 mg/kg/d Lira twice a day for 8 weeks, and the protein expression of phosphorylated AMP kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase 1 (p-ACC1) and UCP1 in white adipose tissues were detected. Differentiated C2C12 cells were treated with palmitic acid (PA) and Lira to detect the secretion of irisin. Differentiated 3T3-L1 cells were treated with irisin, supernatant from Lira-treated C2C12 cells, Compound C or siAMPKα1, the triglyceride (TG) content and the related gene expression were measured. The transcriptome in irisin-treated differentiated 3T3-L1 cells was analyzed. Lira elevated serum irisin levels, decreased the adipocyte size and increased the protein expression of UCP1, p-AMPK and p-ACC1 in WAT. Moreover, it promoted the expression of PGC1α and FNDC5, the secretion of irisin in PA-treated differentiated C2C12 cells. The irisin and supernatant decreased TG synthesis and promoted the expression of browning- and lipolysis-related genes in differentiated 3T3-L1 cells. While Compound C and siAMPKα1 blocked AMPK activities and expression, irisin partly reversed the pathway. Finally, the transcriptome analysis indicated that differently expressed genes are mainly involved in browning and lipid metabolism. Overall, our findings showed that Lira modulated muscle-to-adipose signaling pathways in diabetes via irisin-mediated AMPKα/ACC1/UCP1/PPARα pathway. Our results suggest a new mechanism for the treatment of T2DM by Lira.

Exercise affects high-fat diet-stimulated breast cancer metastasis through irisin secretion by altering cancer stem cell properties

BackgroundRegular physical activities reduce the growth of breast cancer, but research on the effects of steady exercise on metastasis and its mechanisms is limited. In this study, the effects of steady exercise on breast cancer metastasis and its possible mechanism were demonstrated. MethodsExperimental metastasis was induced after 8 weeks of steady exercise using a mouse model. Furthermore, one of the myokines, irisin, was studied to elucidate the effects of metastasis-regulating protein expression, and colony and sphere formation, which are cancer stem cell properties. ResultsLow- and moderate-intensity exercise significantly reduced the number and volume of metastasized tumors. Among myokines, only irisin was significantly increased by steady exercise but decreased by a high-fat diet. In vitro studies, irisin significantly decreased the number of colonies and sphere formation. Irisin also inhibited cell migration and invasion and suppressed the malignancy of breast cancer cells by reducing the expression of vimentin, MMP-2, MMP-9, and HIF-1 and by increasing the expression of TIMP-1 and TIMP-2. ConclusionSteady exercise modulates myokine secretions and among them, irisin suppresses breast cancer metastasis by decreasing self-renewal properties and invasion regulating protein expressions. Thus, regular exercise may be beneficial in the prevention of breast tumor metastasis.

Plasma irisin and the brain-derived neurotrophic factor levels in sedentary subjects: effect of 8-weeks lifestyle intervention.

Objectives. Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2 diabetes, hyper-tension, dyslipidemia, and others. Physical inactivity together with an imbalance in caloric intake and expenditure leads to a loss of muscle mass, reduced insulin sensitivity, and accumulation of the visceral fat. Organokines (adipokines, myokines, hepatokines, etc.) serve in the organism for inter-organ communication. However, human studies focused on the exercise-related changes in plasma levels of certain myokines have produced contradictory results. In the present study, we verified a hypothesis that myokine irisin, which is expected to increase in response to physical activity, induces brain-derived neurotrophic factor (BDNF) production and by this way mediates the beneficial effect of exercise on several brain functions. Subjects and Methods. Women (n=27) and men (n=10) aged 44.5±12.0 years, who were sedentary and overweight/obese (men ≥25%, women ≥28% body fat), participated in the study. The effect of an 8-week intensive lifestyle intervention (150 minutes of moderate physical activity per week, diet modification, and reduction of caloric intake) on the selected organokines (irisin, BDNF) in the context of an expected improvement in cardiometabolic status was examined. Results. The 8-week lifestyle intervention resulted in a significant (p<0.05) reduction in body mass index, body fat, blood pressure, insulin resistance, lipid and liver parameters, and irisin levels (p<0.001). However, BDNF increase in the whole group did not reach statistical significance. After the improvement of cardiometabolic parameters, a significant decrease in irisin and increase in BDNF levels were also observed in the subgroup with unsatisfactory (≤5%) body weight reduction. Neither relationship between irisin and BDNF levels, nor effect of age or sex on their levels was observed. Conclusions. We cannot confirm the hypothesis that exercise-induced irisin may increase the BDNF levels, whereas, the organokine levels in the periphery may not completely reflect the processes in the brain compartments. The observed decrease in irisin levels after 8-week intensive lifestyle intervention program, which was in contrary to its supposed mechanisms of action and dynamics, suggests the presence of several yet undiscovered impacts on the secretion of irisin.

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.

The effect of long-term strength training on serum levels of betatrophin and irisin in elderly men with type 2 diabetes

Background. The irisin and betatrophin hormones are involved in insulin resistance. Considering the muscle weakness of elderly diabetics, this study aimed to investigate the effect of 21 weeks of strength training on betatrophin and irisin serum levels in type 2 diabetic elderly men. Methods. This semi-experimental study was conducted on type 2 diabetic men with an average age of 70.85±2.90 years. The strength training protocol was performed twice a week for 21 weeks. The exercises consisted of three stages: 1- muscle endurance, 2- muscle hypertrophy, and 3- maximum strength training. Fasting blood glucose levels and serum levels of insulin, betatrophin, and irisin were measured in two phases before and after the exercises. Results. The serum levels of insulin, irisin, and betatrophin in the diabetes control group were lower than in the healthy group (P&lt;0.05) and 21 weeks of strength training increased the serum levels of insulin, irisin, and betatrophin, and decreased body weight and fasting blood glucose levels in elderly diabetic men compared to the control group (P&lt;0.05). Conclusion. Strength training improved metabolic disorders in diabetics and increased secretion of irisin and betatrophin following exercise which indicated that exercise may have a protective mechanism in diabetes. Practical Implications. Stationary movements by performing strength activities, through the development of skeletal muscles of diabetics, improve insulin sensitivity and harvest more glucose in the body. In addition, these exercises can be a protective mechanism to prevent or delay the complications of type 2 diabetes by increasing irisin and betatrophin levels.

Abstract P2144: Irisin, An Exercise-induced Myokine, Exhibits Protective Effects In Glucocorticoid-induced Cardiac Muscle Dysfunctions

Myocardial infarction caused by pharmacological substances, such as anti-inflammatory drugs, is a serious adverse drug effect in the cardiovascular system that often causes heart failure. Dexamethasone (DEX), a synthetic glucocorticoid, is commonly used as potent anti-inflammatory and immunosuppressive drugs, but is classified as one of the prime suspects of drug-induced acute myocardial infarction. High dose of DEX increased oxidative stress of the heart, induced myocardial degeneration and cardiomyocyte apoptosis and impaired cardiac contraction. Thus, therapeutic approaches are required to alleviate glucocorticoids-induced cardiotoxicity and prevent DEX-mediated cardiac complications. Exercise-induced secretion of irisin showed the beneficial effects against cardiovascular diseases on energy metabolism, anti-oxidant effects, and decreased inflammation and apoptosis by promoting mitochondria biogenesis, decreasing oxidative stress and inflammatory responses, and regulating intracellular calcium signaling. In this study, we investigate the endocrine effects of muscle-secreted irisin against DEX-induced cardiotoxicity. We engineered anisotropic human induced-pluripotent stem cell-derived cardiomyocyte tissues and designed three experimental groups: control, dex treatment, and dex plus irisin treatment. We then analyze the tissues with qPCR, immunostaining (muscle atrophy markers), contractility assay, and oxygen consumption assay to evaluate the protective effects of irisin on DEX-induced cardiac injury. Injured cardiac tissues showed systolic dysfunction by decreasing oxygen consumption, increasing muscle atrophy marker (MuRF-1), and significantly reducing systolic contractile force, but not diastolic stress. In contrast, these DEX-induced maladaptive responses was alleviated by irisin pretreatment by reducing proteolytic activity and muscle atrophy signaling pathways and promoting mitochondria biogenesis. In conclusion, our micro-physiological system showed the therapeutic effects of irisin against DEX-induced cardiotoxicity.

Irisin and Atherogenic Index of Plasma Novel Markers in Diabetic Patients with and without Metabolic Syndrome

BACKGROUND OF THE STUDY: Skeletal muscle tissue and adipose tissue cells initiate for creating and releasing semi warning protein hormones that are characteristic signals for the possibility of heart attacks, which resulted in hyperglycemia and hyperlipidemia in the blood due to insulin resistance. The study aims to high lighting on the accompany health problems of type 2 diabetes patients with metabolic syndrome (MS). MATERIALS AND METHODS: Ninety males and females were shared in this study, their ages ranged from 40 to 55 years, and they were divided into three groups: 30 were type 2 diabetes mellitus (T2DM) with MS, 30 were T2DM without MS, and 30 were from the group of healthy controls. Enzymatic assays were estimated, and blood samples tests included: fasting serum glucose, glycated hemoglobin, lipid profile total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein, irisin level, and the atherogenic index of plasma (AIP) were calculated. RESULTS: A highly statistically significant increase (P &lt; 0.001) of irisin level (96.80 ± 27.05 ng/mL) was find in patients who had T2DM with MS whom have the highest body mass index and waist value, but irisin level had (67.66 ± 19.41 ng/mL) in T2DM without the MS group. While the normal value of irisin level (27.97 ± 9.29 ng/mL) had be recorded in the control group. CONCLUSION: Irisin secretion is related to MS problems, and the possibility of targeting this hormone as a marker, particularly in the detection of heart diseases. A high AIP value demonstrates an association between elevated irisin levels and the accelerated potential with cardiovascular disease.

Dynamic of irisin secretion change after moderate-intensity chronic physical exercise on obese female.

Exercise is one of the beneficial mediators for the regulation and prevention of obesity through the role of irisin, so it potentially enhances metabolism health. This study aims to investigate the dynamic of irisin secrecy change after chronic exercise in obese females. Thirty-one female adolescents aged 20-22 years enrolled in the study and were given interventions aerobic, resistance, and a combination of aerobic and resistance training. The exercises were performed at moderate-intensity, for 35-40 min per session, and three times a week for four weeks. The measurement of irisin level, IGF-1 level, and bio-anthropometry was carried out before and after the four weeks of exercise. The bio-anthropometry measurement was carried out using seca mBCA 514, while the measurement of insulin-like growth factor 1 (IGF-1) and irisin was completed using an enzyme-linked immunosorbent assay (ELISA). The obtained data were analyzed using a one-way ANOVA test with 5 % significance. Our results indicated higher dynamic of irisin and IGF-1 increases in the group with a combination of aerobic and resistance training exercises than the other two groups with a different exercise. Further, we also observed different dynamics of irisin and IGF-1 level increase (p<0.05). Besides, the irisin was also correlated with the IGF-1 and bio-anthropometric parameters (p<0.05). The combination of aerobic and resistance training exercises is considered as the alternative for enhancing the dynamic of irisin and IGF-1 increase. Thus, itcan be used to prevent and regulate obesity.

Low-intensity pulsed ultrasound triggers a beneficial neuromodulation in dementia mice with chronic cerebral hypoperfusion via activation of hippocampal Fndc5/irisin signaling

BackgroundExercise-related signaling Fndc5/irisin expresses in brain and acts as a crucial regulator of cognitive function, but its detailed roles in vascular dementia (VaD) are still unclear. Low intensity pulsed ultrasound (LIPUS), a novel brain stimulation approach, has been suggested as a promising treatment for dementia. Here, we investigated the activity and efficacy of Fndc5/irisin in experimental VaD, further explored whether the potential effects of LIPUS on VaD is related to Fndc5/irisin.MethodsMouse model of VaD was established with chronic cerebral hypoperfusion (CCH) using bilateral common carotid arteries stenosis (BCAS). Transcranial LIPUS was applied 24 h after BCAS and subsequently daily with a stimulation time of 5 min at an ultrasound pressure of 0.51 MPa for a period of 28 days. The levels of Fndc5/irisin in different brain regions, the hippocampal long-term potentiation and anti-inflammatory cytokines were investigated at day 28 after cognitive evaluation. Global Fndc5 knock-out (F5KO), forced expression or knockdown of Fndc5, and recombinant irisin application were respectively employed for mechanism exploration. The neuron dendritic spine density and astrocyte phenotype were detected in vitro.ResultsFndc5/irisin was reduced in hippocampus of BCAS mice, forced expression hippocampal Fndc5 or bilateral intrahippocampal injection of recombinant irisin respectively improved hippocampal synaptic plasticity or inflammatory microenvironment, and then alleviated the cognitive impairments. LIPUS existed a positive efficacy in enhancing hippocampal Fndc5/irisin in BCAS mice, thus triggering a beneficial neuromodulation for VaD protection. Importantly, the neurorestorative effects of LIPUS on CCH-induced damages were totally reversed by knockdown the expression of hippocampal Fndc5 in WT mice, or in F5KO mice. Moreover, Fndc5 mediated the upregulated effects of LIPUS on spine density as well as irisin secretion of hippocampal neurons. The neuron-secreted irisin further drove reactive astrocytes to a neuroprotective phenotype.ConclusionLIPUS induced a neurorestorative stimulation against VaD may be through upregulation of the hippocampal Fndc5/irisin levels. Hippocampal Fndc5/irisin signaling might be a promising strategic target for VaD.

Irisin modulates glucose metabolism and inhibits steroidogenesis in bovine granulosa cells.

Fertility in the dairy cow is low during the post-partum period of negative energy balance and high plasma irisin concentrations. This study shows irisin modulates granulosa cell glucose metabolism and impairs steroidogenesis. Fibronectin type III domain-containing 5 (FNDC5) is a transmembrane protein discovered in 2012 that is cleaved to release the adipokine-myokine, irisin. Originally described as an exercise hormone that browns white adipose tissue and increases glucose metabolism, irisin secretion also increases during periods of rapid adipose mobilization, such as the post-partum period in dairy cattle when ovarian activity is suppressed. The effect of irisin on follicle function is unclear and may be species-dependent. In this study, we hypothesized that irisin may compromise granulosa cell function in cattle using a well-established in vitro cell culture model. We detected FNDC5 mRNA and both FNDC5 and cleaved irisin proteins in follicle tissue and in follicular fluid. The abundance of FNDC5 mRNA was increased by the treatment of cells with the adipokine visfatin but not by other adipokines tested. The addition of recombinant irisin to granulosa cells decreased basal and insulin-like growth factor 1- and follicle-stimulating hormone-dependent estradiol and progesterone secretion and increased cell proliferation but had no effect on viability. Irisin decreased GLUT1, GLUT3, and GLUT4 mRNA levels in granulosa cells and increased lactate release in the culture medium. The mechanism of action is in part through MAPK3/1 but not Akt, MAPK14, or PRKAA. We conclude that irisin may regulate bovine folliculogenesis by modulating granulosa cell steroidogenesis and glucose metabolism.

The Association of Serum Irisin with Impaired Glucose Before and After Laparoscopic Sleeve Gastrectomy in Obesity.

To demonstrate the association of irisin levels with impaired glucose before and after laparoscopic sleeve gastrectomy (LSG) in patients with obesity. Thirty-six patients with obesity undergoing LSG were included. We tested the irisin levels before and after LSG and conducted an evaluation of baseline irisin levels with elevated glucose as well as irisin changes with weight loss and its association with glucose control after LSG. Anthropometric measurements, body fat index, and metabolic parameters were significantly improved in 3months following LSG (all p < 0.05). Baseline irisin levels were significantly higher in obesity with elevated fasting glucose than that with normal glucose (2.98 [2.37, 3.63] vs. 3.72 [3.06, 5.32], p = 0.031). After adjustment for sex, gender, and body mass index (BMI), obesity with higher irisin levels was prone to have impaired fasting glucose (OR = 2.499, 95% CI = 1.047-5.964). According to receiver operating characteristic curve analysis, the diagnostic accuracy and sensitivity of baseline irisin levels on impaired fasting glucose were 75% and 77.8%. Irisin levels decreased from 3.29 (2.67, 4.43) to 2.82 (2.41, 3.25) ng/mL (p = 0.009) after LSG. The decreases of weight, BMI, and FFA were more in irisin changes group (△irisin ≥ 0.5) than in no irisin changes group (△irisin < 0.5). And △irisin was negatively associated with postprandial glucose (PG) at 3months after LSG (0.5h-PG, r = - 0.478, p = 0.029; 2h-PG, r = - 0.406, p = 0.017). Elevated baseline irisin levels indicated the impaired glucose in obesity. The decrease of irisin with weight loss provided more evidence for the contribution of serum irisin secretion by fat mass in obesity.

The Effect of Exercise Training on Irisin Secretion in Patients with Type 2 Diabetes: A Systematic Review

Irisin is a myokine considered to be a potential mediator of exercise-induced energy metabolism and its secretion is known to promote the browning of beige fat cells in white adipose tissue. However, it is currently not known which exercise protocol is the best to enhance irisin concentration in patients with type 2 diabetes (T2D). The purpose of this study is to provide a review investigating the irisin response to different exercise training modalities and intensities in T2D. A systematic literature search was performed in May 2022. After the selection process from 938 articles, six studies were included. Selected papers presented different exercise training interventions regarding intensity and modality. One study reported no significant differences in serum irisin levels after exercise training, whereas the other five showed a higher increase in serum irisin levels after exercise training with higher differences in irisin secretion after high-intensity training (HIT). No consideration was possible on exercise modalities. The impact of training intensity and modality was found to be partly discordant but data seem to suggest that HIT promotes greater irisin secretion. Despite the limited evidence, HIT, both in interval and continuous modalities, could be suggested as valid exercise training to increase circulating irisin in patients with T2D.