Role Of Irisin Research Articles

Cardioprotective Effects of Exercise: The Role of Irisin and Exosome.

Exercise is an effective measure for preventing and treating cardiovascular diseases, although the exact molecular mechanism remains unknown. Previous studies have shown that both irisin and exosomes can improve the course of cardiovascular disease independently. Therefore, it is speculated that the cardiovascular protective effect of exercise is also related to its ability to regulate the concentrations of irisin and exosomes in the circulatory system. In this review, the potential synergistic interactions between irisin and exosomes are examined, as well as the underlying mechanisms including the AMPK/PI3K/AKT pathway, the TGFβ1/Smad2/3 pathway, the PI3K/AKT/VEGF pathway, and the PTEN/PINK1/Parkin pathway are examined. This paper provides evidence to propose that exercise promotes the release of exosomes enriched with irisin, miR-486-5p and miR-342-5p from skeletal muscles, which results in the activation protective networks in the cardiovascular system. Moreover, the potential synergistic effect in exosomal cargo can provide new ideas for clinical research of exercise mimics.

Irisin Ameliorate Acute Pancreatitis and Acinar Cell Viability through Modulation of the Unfolded Protein Response (UPR) and PPARγ-PGC1α-FNDC5 Pathways.

Acute pancreatitis (AP) entails pancreatic inflammation, tissue damage and dysregulated enzyme secretion, including pancreatic lipase (PL). The role of irisin, an anti-inflammatory and anti-apoptotic cytokine, in AP and exocrine pancreatic stress is unclear. We have previously shown that irisin regulates PL through the PPARγ-PGC1α-FNDC5 pathway. In this study, we investigated irisin and irisin's pathway on AP in in vitro (AR42J-B13) and ex vivo (rat primary acinar) models using molecular, biochemical and immunohistochemistry methodology. Pancreatitis induction (cerulein (cer)) resulted in a significant up-regulation of the PPARγ-PGC1α-FNDC5 axis, PL expression and secretion and endoplasmic reticulum (ER) stress unfolded protein response (UPR) signal-transduction markers (CHOP, XBP-1 and ATF6). Irisin addition in the cer-pancreatitis state resulted in a significant down-regulation of the PPARγ-PGC1α-FNDC5 axis, PPARγ nucleus-translocation and inflammatory state (TNFα and IL-6) in parallel to diminished PL expression and secretion (in vitro and ex vivo models). Irisin addition up-regulated the expression of pro-survival UPR markers (ATF6 and XBP-1) and reduced UPR pro-apoptotic markers (CHOP) under cer-pancreatitis and induced ER stress (tunicamycin), consequently increasing cells viability. Irisin's pro-survival effect under cer-pancreatitis state was abolished under PPARγ inhibition. Our findings suggest irisin as a potential therapeutic option for AP via its ability to up-regulate pro-survival UPR signals and activate the PPARγ-PGC1α-FNDC5 pathway.

Irisin and Its Role in Postmenopausal Osteoporosis and Sarcopenia.

Menopause, an extremely delicate phase in a woman's life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia.

MYOKINE FUNDC5 COMPROMISES MITOCHONDRIAL DYSFUNCTION IN OSTEOARTHRITIS

Chondrocytic activity is downregulated by compromised autophagy and mitochondrial dysfunction to accelerate the development of osteoarthritis (OA). Irisin is a cleaved form of fibronectin type III domain containing 5 (FNDC5) and known to regulate bone turnover and muscle homeostasis. However, little is known about the role of irisin in chondrocytes and the development of OA. This talk will shed light on FNDC5 expression by human articular chondrocytes and compare normal and osteoarthritic cells with respect to autophagosome marker LC3-II and oxidative DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG). In chondrocytes in vitro, irisin improves IL-1β-mediated growth inhibition, loss of specific cartilage markers and glycosaminoglycan production. Irisin further suppressed Sirt3 and UCP- 1 to improve mitochondrial membrane potential, ATP production, and catalase. This attenuated IL-1β-mediated production of reactive oxygen species, mitochondrial fusion, mitophagy, and autophagosome formation. In a surgical murine model of destabilization of the medial meniscus (DMM) intra-articular administration of irisin alleviates symptoms like cartilage erosion and synovitis. Furthermore, gait profiles of the treated limbs improved. In chondrocytes, irisin treatment upregulates autophagy, 8-OHdG and apoptosis in cartilage of DMM limbs. Loss of FNDC5 in chondrocytes correlates with human knee OA and irisin repressed inflammation-mediated oxidative stress and deficient extracellular matrix synthesis through retaining mitochondrial biogenesis and autophagy. The talk sheds new light on the chondroprotective actions of this myokine and highlights the remedial effects of irisin during progression of OA.

The role of irisin in predicting obstructive sleep apnea severity among obese individuals: a comparative analysis.

This study aimed to investigate the predictive value of circulating irisin levels in discriminating the presence and severity of obstructive sleep apnea (OSA) in obese individuals. This study was conducted on obese volunteers with and without OSA. All volunteers underwent polysomnography. Blood samples were taken on the day of the test. In addition to routine biochemistry studies, irisin levels were determined by enzyme-linked immunosorbent measurement. ROC analysis was performed to determine the predictive value of irisin. Of 100 volunteers, 75 had OSA and 25 did not. Irisin levels were significantly lower in the group with OSA than in thenon-OSAgroup. The lowest irisin levels were determined in the group withsevere OSA. Irisin levels showed high sensitivity and specificity in distinguishing between OSA and non-OSA groups. It had high sensitivity and specificity in differentiating severe OSA from other groups in subgroups, while it had low sensitivity and specificity in differentiating patients withmild and moderate OSA. In logistic regression analysis, alow irisin level was determined to be a risk factor for OSA independent of BMI. This study indicated that irisin levels decrease in obese individuals with OSA, correlating with the severity of the condition. Additionally, irisin levels may act as an independent predictor for OSA. The predictive value of irisin in identifying severe OSA among obese patients suggests its potential as a promising biomarker.

Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome.

Irisin is a thermogenic hormone that leads to causes energy expenditure by increasing brown adipose tissue (BAT). This protein hormone that enables the conversion of white adipose tissue (WAT) to BAT is the irisin protein. This causes energy expenditure during conversion. WAT stores triglycerides and fatty acids and contains very few mitochondria. They also involve in the development of insulin resistance (IR). WAT, which contains a very small amount of mitochondria, contributes to the formation of IR by storing triglycerides and fatty acids. WAT functions as endocrine tissue in the body, synthesizing various molecules such as leptin, ghrelin, NUCB2/nesfatin-1, and irisin along with fat storage. BAT is quite effective in energy expenditure, unlike WAT. The number of mitochondria and lipid droplets composed of multicellular cells in BAT is much higher when compared to WAT. BAT contains a protein called uncoupling protein-1 (UCP1) in the mitochondrial membranes. This protein pumps protons from the intermembrane space toward the mitochondrial matrix. When UCP1 is activated, heat dissipation occurs while ATP synthesis does not occur, because UCP1 is a division protein. At the same time, BAT regulates body temperature in infants. Its effectiveness in adults became clear after the discovery of irisin. The molecular mechanism of exercise, which increases calorie expenditure, became clear with the discovery of irisin. Thus, the isolation of irisin led to the clarification of metabolic events and fat metabolism. In this review, literature information will be given on the effect of irisin hormone on energy metabolism and metabolic syndrome (MetS).

Roles of Irisin, a Myokine on Uremic Sarcopenia

Roles of Irisin, a Myokine on Uremic Sarcopenia

Role of irisin in bone diseases.

Bone diseases are common among middle-aged and elderly people, and harm to activities of daily living (ADL) and quality of life (QOL) for patients. It is crucial to search for key regulatory factors associated with the development of bone diseases and explore potential therapeutic targets for bone diseases. Irisin is a novel myokine that has been discovered in recent years. Accumulating evidence indicates that irisin has beneficial effects in the treatment of various diseases such as metabolic, cardiovascular and neurological disorders, especially bone-related diseases. Recent studies had shown that irisin plays the role in various bone diseases such as osteoarthritis, osteoporosis and other bone diseases, suggesting that irisin may be a potential molecule for the prevention and treatment of bone diseases. Therefore, in this review, by consulting the related domestic and international literature of irisin and bone diseases, we summarized the specific regulatory mechanisms of irisin in various bone diseases, and provided a systematic theoretical basis for its application in the diagnosis and treatment of the bone diseases.

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.

Anti-obesity effects of aerobic exercise along with Rosa canina seed extract supplementation in rats: The role of irisin and adipolin

Aerobic exercise and some bioactive compounds in medicinal plants have anti-obesity effects and can suppress body weight. The aim of this study was to determine the anti-obesity effects of 6 weeks of aerobic exercise (AE) and supplementation of the hydroalcoholic extract of Rosa canina fruit seed (RC) in obese male rats. In this experimental study, 24 high-fat diet (HFD) obese male Wistar rats were used. The animals were randomly divided into 4 groups (6 rat in group), including 1. HFD (the control group), 2. HFD + AE, 3. HFD + RC and 4. HFD + AE + RC. An obesity protocol was implemented for 12 weeks with the consumption of HFD along with the consumption of water containing 1 % fructose. Afterwards, the animals were given access only to HFD food until the end of the study in all the groups. After the obesity protocol, 6 weeks of exercise (50–70 % VO2 max) and access to the extract (1 % of the consumed food) were given. Bodyweight, subcutaneous adipose tissue mass, and some serum lipid profiles were measured in the experimental groups. The serum levels of irisin and adipolin were evaluated by the ELISA method. Expression of FNDC5 and CTRP12 in adipose tissue were determined by real-time PCR. The findings of this study showed that body weight (P = 0.001), subcutaneous adipose tissue mass (P = 0.001), and lipid profile were significantly reduced in HFD + AE and HFD + AE + RC groups compared with the HFD group. Irisin was significantly increased in the HFD + AE and HFD + AE + RC groups compared with the HFD group (P = 0.019 and P = 0.001; respectively) and in the HFD + AE + RC group compared with the HFD + RC group (P = 0.004). Moreover, adipolin, expression of FNDC5 and CTRP12 were significantly increased in the HFD + AE + RC group compared with the HFD group (P = 0.004, P = 0.023, and P = 0.001; respectively). Altogether, HFD + AE with HFD + RC diet supplementation could reduce weight and the risks of obesity, at least, through the up-regulation of irisin and adipolin.

Role of Irisin in Physiological and Pathological Conditions: Review Article

Role of Irisin in Physiological and Pathological Conditions: Review Article

The role of irisin and asprosin level in the pathophysiology of prediabetes

PurposeWe aimed to examine whether irisin and asprosin have a role in the physiopathology of prediabetes. MethodsHundred people were selected between the age of 18–65 years for the study population (60 prediabetes, 40 healthy). For the follow-up study, the patients with prediabetes were offered a 3-month program for lifestyle change and then reevaluated. Our research is a single-center, prospective observational study. ResultsAmong the healthy group and patients with prediabetes, irisin levels were lower and asprosin levels were higher (p < 0.001) in patients. In the follow-up part, the patients’ insulin levels, HOMA index scores, and asprosin levels were decreased while irisin levels were elevated (p < 0.001). Sensitivity was 98.3% and specificity was 65% for asprosin of > 56.3 ng/mL, while they were 93.3% and 65% for irisin of ≤ 120.2 pg/mL, respectively. It was found that irisin had diagnostic performance similar to insulin and the HOMA index, while asprosin performed similarly to glucose, insulin, and the HOMA index. ConclusionBoth irisin and asprosin have been found to be related to the prediabetes pathway and it has been shown that these molecules may be useful in daily clinical practice with diagnostic performances similar to those of the HOMA index and insulin.

Irisin attenuates fine particulate matter induced acute lung injury by regulating Nod2/NF-κB signaling pathway

Air pollution consisting of fine particulate matter (PM2.5) can induce or aggravate pulmonary inflammatory injury. Irisin has been shown to inhibit inflammation and help to protect against acute kidney, lung or brain injury. However, the role of irisin in lung inflammation after exposure to PM2.5 remains unclear. The aim of this study was to investigate the effect and molecular mechanism of irisin supplementation on in vitro and in vivo models of PM2.5-induced acute lung injury（ALI). C57BL/6 mice and alveolar macrophage cell line (MH-S) were treated with PM2.5. Histopathological examination and FNDC5/ irisin immunofluorescence staining was performed on lung tissue sections. MH-S cell viability was determined by CCK-8 assay. The levels of Nod2, NF-κB p65 and NLRP3 were detected by qRT-PCR and western blotting. The levels of cytokines (IL-1β, IL-18 and TNF-α) were detected by ELISA. PM2.5 exposure induced increased secretion of pro-inflammatory factors and activation of Nod2, NF-κB p65 and NLRP3 as well as endogenous levels of irisin. In vivo and in vitro inflammation was alleviated by irisin supplementation. Irisin significantly decreased IL-1β, IL-18, and TNF-α production at both mRNA and protein level. Expression levels of Nod2, NF-κB p65, and NLRP3 were all significantly affected by irisin. In vivo the degree of pulmonary injury and inflammatory infiltration was weakened after irisin administration. In vitro, irisin could inhibit the activation of the NLRP3 inflammasome for a sustained period of 24 h, and its inhibitory ability was gradually enhanced. In conclusion, our findings indicate that irisin can modulate the inflammatory injury of lung tissue caused by PM2.5 through the Nod2/NF-κB signaling pathway, suggesting that irisin can be a candidate for the therapeutic or preventive intervention in acute lung inflammation.

Non-thyroidal illness syndrome in chronic diseases: role of irisin as modulator of antioxidants.

Non-thyroidal-illness syndrome (NTIS) refers to condition found in chronic diseases that is an adaptive mechanism. However, oxidative stress is related to NTIS in a vicious circle, due to deiodinases alteration and negative effects of low T3 on antioxidant levels or activity. Muscle is one of the main targets of thyroid hormones and it can secrete a myokine named irisin, which is able to induce the browning of white adipose tissue, energy expenditure and protect against insulin resistance. Inconclusive data have been reported about irisin role in chronic diseases. Moreover, no correlation with antioxidants has been investigated. Therefore, we performed a case-control study with the primary endpoint to evaluate irisin levels in two models of NTIS, such as chronic heart failure (CHF) and chronic kidney disease (CKD) during haemodialytic treatment. The secondary endpoint was the correlation with total antioxidant capacity (TAC) to establish a possible role of irisin in the modulation of antioxidant systems. Three groups of subjects were enrolled. Group A included CHF patients (n=18; aged 70.22 ± 2.78 ys; BMI ± 27.75 ± 1.28 kg/m2); Group B included CKD patients (n=29; aged 67.03 ± 2.64; BMI 24.53 ± 1.01); finally, 11 normal subjects (Group C) have been enrolled as controls. Irisin has been evaluated by ELISA method and Total Antioxidant Capacity (TAC) by spectrophotometric method. Irisin was significantly higher in Group B vs. A and C groups (Mean ± SEM: 20.18 ± 0.61 ng/ml vs. 2.77 ± 0.77 and 13.06 ± 0.56, respectively; p<0.05); a significant correlation between irisin and TAC was observed in group B. These preliminary data suggest a possible role of irisin in the modulation of antioxidants in two chronic syndromes with low T3 (i.e., CHF and CKD) with differential pattern in these two models studied. Further insights are needed to confirm this pilot study, which could be the basis for a longitudinal investigation, to assess a prognostic role of irisin with possible therapeutic implications.

Cerebrospinal fluid irisin and lipoxin A4 are reduced in elderly Brazilian individuals with depression: Insight into shared mechanisms between depression and dementia.

Depression is frequent among older adults and is a risk factor for dementia. Identifying molecular links between depression and dementia is necessary to shed light on shared disease mechanisms. Reduced brain-derived neurotrophic factor (BDNF) and neuroinflammation are implicated in the pathophysiology of depression and dementia. The exercise-induced hormone, irisin, increases BDNF and improves cognition in animal models of Alzheimer's disease. Lipoxin A4 is a lipid mediator with anti-inflammatory activity. However, the roles of irisin and lipoxin A4 in depression remain to be determined. In the present study, blood and CSF were collected from 61 elderly subjects, including individuals with and without cognitive impairment. Screening for symptoms of depression was performed using the 15-item Geriatric Depression Scale (GDS-15). CSF irisin and lipoxin A4 were positively correlated and reduced, along with a trend of BDNF reduction, in elderly individuals with depression, similar to previous observations in patients with dementia. Our findings provide novel insight into shared molecular signatures connecting depression and dementia.

The effects of irisin on the rat thoracic aorta: a histological study.

Irisin, a polypeptide hormone that is released from skeletal muscle in response to exercise, has been found to improve endothelial functions, protect against endothelial injuries and change blood pressure, which also affected blood vessels. The aim of this study was to assess the histological changes of the rat thoracic aorta in response to irisin injection. Twenty-four rats were used. They were divided into two groups: the control group without irisin injection and the irisin-injected group subdivided into three subgroups treated with different irisin concentrations (20, 40 and 160 nM, respectively) twice a week for 4 weeks. The control group and irisin-treated subgroups consisted of 6 rats each. After 4 weeks all rats were sacrificed, and the descending thoracic aorta was treated for histological evaluation. Sections were stained with haematoxylin and eosin and orcein stains. Morphometric measurement included: intima-media thickness, number of elastic lamellae and number of smooth muscle cells' nuclei. Histological study showed that intraperitoneal injection of different concentrations of irisin (20, 40 and 160 nM) in rats increased intima-media thickness, the number of smooth muscle cell's nuclei and the number of elastic lamellae in media layer of the thoracic aorta in a dose-dependent manner. Irisin significantly affected the morphology of the wall of the rat thoracic aorta indicating a role of irisin in influencing the growth factors of the thoracic aorta walls and activating smooth muscle cells in the thoracic aorta layers.

Irisin Promotes Osteogenesis by Modulating Oxidative Stress and Mitophagy through SIRT3 Signaling under Diabetic Conditions.

Advanced glycation end products (AGEs) accumulate in the bone tissue of patients with diabetes mellitus, resulting in oxidative stress, poor bone healing, or regeneration. Irisin, a novel exercise-induced myokine, is involved in the regulation of bone metabolism. However, the effects of irisin on adipose-derived stem cell (ASC) osteogenic differentiation and bone healing under diabetic conditions remain poorly understood. ASCs were obtained from inguinal fat of Sprague-Dawley rats and treated with different concentrations of AGEs and irisin. Cell proliferation, apoptosis, and osteogenic differentiation abilities of ASCs were detected. To explore the regulatory role of sirtuin 3 (SIRT3), ASCs were transfected with lentivirus-mediated SIRT3 overexpression or knockdown vectors. Next, we investigated mitochondrial functions, mitophagy, and mitochondrial biogenesis in different groups. Moreover, SOD2 acetylation and potential signaling pathways were assessed. Additionally, a diabetic rat model was used to evaluate the effect of irisin on bone healing in calvarial critical-sized defects (CSDs) in vivo. Our results showed that irisin incubation mitigated the inhibitory effects of AGEs on ASCs by increasing cell viability and promoting osteogenesis. Moreover, irisin modulated mitochondrial membrane potential, intracellular ROS levels, mitochondrial O2·− status, ATP generation, complex I and IV activities, mitophagy, and mitochondrial biogenesis via a SIRT3-mediated pathway under AGEs exposure. Furthermore, in calvarial CSDs of diabetic rats, transplantation of gels encapsulating irisin-pretreated ASCs along with irisin largely enhanced bone healing. These findings suggest that irisin attenuates AGE-induced ASC dysfunction through SIRT3-mediated maintenance of oxidative stress homeostasis and regulation of mitophagy and mitochondrial biogenesis. Thus, our studies shed new light on the role of irisin in promoting the ASC osteogenesis and targeting SIRT3 as a novel therapeutic intervention strategy for bone regeneration under diabetic conditions.

Role of irisin in physiology and pathology.

Irisin, out-membrane part of fibronectin type III domain–containing 5 protein (FNDC5), was activated by Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) during physical exercise in skeletal muscle tissues. Most studies have reported that the concentration of irisin is highly associated with health status. For instance, the level of irisin is significantly lower in patients with obesity, osteoporosis/fractures, muscle atrophy, Alzheimer’s disease, and cardiovascular diseases (CVDs) but higher in patients with cancer. Irisin can bind to its receptor integrin αV/β5 to induce browning of white fat, maintain glucose stability, keep bone homeostasis, and alleviate cardiac injury. However, it is unclear whether it works by directly binding to its receptors to regulate muscle regeneration, promote neurogenesis, keep liver glucose homeostasis, and inhibit cancer development. Supplementation of recombinant irisin or exercise-activated irisin might be a successful strategy to fight obesity, osteoporosis, muscle atrophy, liver injury, and CVDs in one go. Here, we summarize the publications of FNDC5/irisin from PubMed/Medline, Scopus, and Web of Science until March 2022, and we review the role of FNDC5/irisin in physiology and pathology.

Exercise-induced modulation of myokine irisin in bone and cartilage tissue-Positive effects on osteoarthritis: A narrative review.

Osteoarthritis is a chronic degenerative musculoskeletal disease characterized by pathological changes in joint structures along with the incidence of which increases with age. Exercise is recommended for all clinical treatment guidelines of osteoarthritis, but the exact molecular mechanisms are still unknown. Irisin is a newly discovered myokine released mainly by skeletal muscle in recent years—a biologically active protein capable of being released into the bloodstream as an endocrine factor, the synthesis and secretion of which is specifically induced by exercise-induced muscle contraction. Although the discovery of irisin is relatively recent, its role in affecting bone density and cartilage homeostasis has been reported. Here, we review the production and structural characteristics of irisin and discuss the effects of the different types of exercise involved in the current study on irisin and the role of irisin in anti-aging. In addition, the role of irisin in the regulation of bone mineral density, bone metabolism, and its role in chondrocyte homeostasis and metabolism is reviewed. A series of studies on irisin have provided new insights into the mechanisms of exercise training in improving bone density, resisting cartilage degeneration, and maintaining the overall environmental homeostasis of the joint. These studies further contribute to the understanding of the role of exercise in the fight against osteoarthritis and will provide an important reference and aid in the development of the field of osteoarthritis prevention and treatment.

Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis.

IntroductionPatients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients.MethodsA large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA.ResultsLow irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p<0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p<0.05 in all the cases). Moreover, lower irisin levels were observed in patients with sacroiliitis and in those with a negative HLA-B27 status (p<0.001 and p=0.006, respectively), as well as in those treated with non-steroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs (p<0.001 and p=0.002, respectively). Interestingly, the TT genotype and the T allele of rs16835198 were less frequent in axSpA patients with ASDAS >2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01).ConclusionsOur results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.