Role Of Irisin Research Articles

The role of irisin in the relationship between psoriasis and insulin resistance.

Irisin, a hormone like myokine, is identified to the relation with insulin resistance and metabolic syndrome recently. In the literature to date, there are no studies evaluating serum irisin levels in psoriasis patients. We aimed to elucidate the pathogenesis of insulin resistance in psoriasis patients by evaluating serum irisin levels and metabolic parameters associated with insulin resistance in patients with plaque-type psoriasis vulgaris. The study included 40 patients with moderate-to-severe chronic plaque-type psoriasis vulgaris and 37 healthy subjects. Body Mass Index (BMI) and waist circumference were measured, and serum irisin, fasting blood glucose (FBG), lipid profile, high-sensitivity CRP (hs-CRP) and insulin levels were assessed. To evaluate insulin resistance, the Homeostasis Model Assessment (HOMA-IR) and triglyceride/HDL (TG/HDL) ratio were used. Serum irisin and HDL levels were significantly lower in patients than the control group (P<0.001, P=0.024). Within the patient group, there was a significant negative correlation between serum irisin and serum TG, LDL, and TG/HDL levels (P=0.041, P=0.022, P=0.025), and a positive correlation with HDL levels (P=0.036). The PASI scores and serum irisin levels were significantly positively correlated. In conclusion, we observed that serum irisin levels were significantly lower in patients with psoriasis, and associated with serum lipid levels and disease activity in our study. These results can be interpreted that irisin is involved in the disease pathogenesis of patients with psoriasis in relation to metabolic dysregulation.

Central inhibitory effects on feeding induced by the adipo-myokine irisin

Irisin, the soluble secreted form of fibronectin type III domain containing 5 (FNDC5)-cleaved product, is a recently identified adipo-myokine that has been indicated as a possible link between physical exercise and energetic homeostasis. The co-localization of irisin with neuropeptide Y in hypothalamic sections of paraventricular nucleus, which receives NPY/AgRP projections from the arcuate nucleus, suggests a possible role of irisin in the central regulation of energy balance. In this context, in the present work we studied the effects of intra-hypothalamic irisin (1μl, 50–200nmol/l) administration on feeding and orexigenic [agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and anorexigenic [cocaine and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC)] peptides in male Sprague-Dawley rats. Furthermore, we evaluated the effects of irisin on hypothalamic dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) concentrations and plasma NE levels. Compared to vehicle, irisin injected rats showed decreased food intake, possibly mediated by stimulated CART and POMC and inhibited DA, NE and orexin-A, in the hypothalamus. We also found increased plasma NE levels, supporting a role for sympathetic nervous system stimulation in mediating increased oxygen consumption by irisin.

Irisin Inhibits Atherosclerosis by Promoting Endothelial Proliferation Through microRNA126-5p.

BackgroundIrisin is a newly discovered myokine that has been considered a promising candidate for the treatment of cardiovascular disease through improving endothelial function. However, little is known about the role of irisin in the progression of atherosclerosis.Methods and ResultsWe used a carotid partial ligation model of apolipoprotein E–deficient mice fed on a high‐cholesterol diet to test the anti‐atherosclerosis effect of irisin. Irisin treatment significantly suppressed carotid neointima formation. It was associated with increased endothelial cell proliferation. In addition, irisin promoted human umbilical vein endothelial cell survival via upregulating microRNA126‐5p expression through the ERK signaling pathway. Inhibition of microRNA126‐5p using the microRNA126‐5p inhibitor abolished the prosurvival effect. The same results were demonstrated in vivo as the expression of microRNA126‐5p noticeably increased in ligated carotid artery after irisin treatment. Furthermore, in vivo blockade of microRNA126‐5p expression using the antagomir abolished the inhibitory effects of irisin on neointima formation, lesional lipid deposition, macrophage area, and the pro‐proliferation effects on endothelial cells.ConclusionsTaken together, our study demonstrates that irisin significantly reduces atherosclerosis in apolipoprotein E–deficient mice via promoting endothelial cell proliferation through microRNA126‐5p, which may have a direct therapeutic effect on atherosclerotic diseases.

Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults.

BackgroundEvidence on the role of irisin in insulin resistance is limited and controversial, and pathways between them remain unknown. We aimed to examine the independent effects of circulating irisin and different adiposity measurements, as well as their potential interactions, on insulin resistance. We also aimed to explore possible pathways among circulating irisin, adiposity, glucose and insulin levels and insulin resistance.MethodsA cross-sectional study of 1,115 community- living obese Chinese adults, with data collection on clinical characteristics, glucose and lipid metabolic parameters and circulating irisin levels.ResultsAmong the 1,115 subjects, 667 (59.8 %) were identified as insulin-resistance, and showed significantly decreased serum irisin than their controls (log-transformed irisin: 1.19 ± 2.34 v.s. 1.46 ± 2.05 ng/ml, p = 0.042). With adjustment for potential confounders, elevated circulating irisin was significantly associated with reduced risk of insulin resistance, with adjusted odds ratio per standard deviation increase of irisin of 0.871 (0.765–0.991, p = 0.036). As for different adiposity measurements, body fat percentage, but neither BMI nor waist, was significantly associated with increased risk of insulin resistance (OR: 1.152 (1.041–1.275), p = 0.006). No significant interaction effect between serum irisin and adiposity on insulin resistance was found. A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ2 = 44.09, p < 0.001; CFI–0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = −0.046, p = 0.032).ConclusionsElevated circulating irisin is associated with lower risk of insulin resistance indirectly through lowering fasting insulin.

Relation of serum irisin level with metabolic and antropometric parameters in obese children

ObjectiveThis study aimed to investigate the relationship between serum irisin level and metabolic and anthropometric parameters in obese children. MethodsThe study included 36 obese children with a body mass index (BMI) of ≥95th percentile and 30 healthy children with a BMI ranging from the 5th to the 85th percentile. Healthy and obese children had similar age, gender and pubertal stage distribution. Anthropometric and biochemical parameters (fasting glucose, insulin, lipid profile, leptin and irisin levels) were measured. Bioelectric impedance analysis was used to determine the body composition parameters, including body fat percentage and fat mass. ResultsSerum irisin and leptin levels of the obese children were significantly higher than those of the healthy children [median irisin levels, 141.2 & 107.6ng/mL, p=0.024; median leptin levels, 10.9 & 2.9pg/mL, P<0.001, respectively). No statistically significant difference was found when leptin and irisin levels were compared among obese patients in terms of the presence of insulin resistance. Irisin levels significantly correlated with high-density lipoprotein cholesterol (HDL-C), fasting insulin and homeostasis model assessment-insulin resistance (HOMA-IR) with adjustment for age and BMI. The multivariate regression analysis showed that age, HOMA-IR and HDL-C had a significant association with the serum irisin level, which explained 30.6% of the variance. ConclusionThis study demonstrated that obese children had significantly higher irisin levels than healthy children. Additionally, it provides evidence regarding the role of irisin on insulin sensitivity and lipid metabolism in childhood obesity.

Adropin and irisin levels in relation to nutrition, body composition, and insulin resistance in patients with end-stage renal disease on chronic hemodialysis and peritoneal dialysis.

INTRODUCTION Newly discovered myokines, adropin, and irisin, are regulators of energy homeostasis and metabolism in humans. In end-stage renal disease (ESRD), the significance and role of irisin and adropin as metabolism regulators are still unclear. OBJECTIVES The aim of this study was to evaluate serum adropin and irisin levels and establish their relation to insulin resistance, nutritional status, and hydration status in patients on chronic hemodialysis (HD) and on peritoneal dialysis (PD). PATIENTS AND METHODS The study consisted of 71 subjects, including 48 patients (18 women, 30 men; median age, 56.5 years; range, 26-84 years) either on HD (n = 41) or PD (n = 7) and 36 healthy controls matched for age and sex. We measured the serum levels of adropin, irisin, creatinine, albumin, glucose, and insulin, as well as the plasma levels of lipids. The bioimpedance method was used to evaluate the body composition and overhydration in patients with ESRD. RESULTS Irisin levels were significantly lower in patients with ESRD compared with controls, but there were no differences in adropin levels between both study groups. Adropin levels were inversely correlated with body mass, lean tissue mass, total, intracellular, and extracellular water, and albumin concentrations in patients with ESRD. Irisin levels were positively correlated with glucose levels and homeostasis model assessment of insulin resistance. No significant correlations were observed between adropin and irisin concentrations and overhydration. CONCLUSIONS Adropin may be considered as a new marker of nutritional status in patients with ESRD. The significance and cause of low irisin levels characteristic for these patients are still unclear. Adropin and irisin should be further investigated as possible markers of cachexia and insulin resistance in patients with ESRD.

Role of Irisin on the bone-muscle functional unit.

Irisin was originally recognized as a hormone-like myokine secreted as a product of fibronectin type III domain containing 5 from skeletal muscle in response to exercise both in mice and humans. The first role attributed to Irisin was its ability to induce trans-differentiation of white adipose tissue into brown, but we recently demonstrated that Irisin also has a central role in the control of bone mass, even at lower concentration than required to induce the browning response. Considering how physical exercise is important for the development of an efficient load-bearing skeleton, we can now consider this myokine as one of the molecules responsible for the positive correlation between exercise and healthy bone, linking to the well-established relationship between muscle and bone. Recombinant Irisin (r-Irisin), administered at low dose in young mice, increases cortical bone mineral density and positively modifies bone geometry. Irisin exerts its effect prevalently on osteoblast lineage by enhancing differentiation and activity of bone-forming cells, through the increase in activating transcription factor 4 expression. Low-dose r-Irisin also increases osteopontin and decreases sclerostin synthesis but did not affect Uncoupling protein 1 expression in white adipose tissue, whose upregulation is known to cause browning of fat, when Irisin is administered at a higher dose. These findings offer an explanation to the positive outcome on the skeleton triggered by skeletal muscle during physical activity and prove that the bone tissue is more sensitive than the adipose tissue to the Irisin action.

Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2.

Irisin, a novel myokine, has been shown to increase following vigorous exercise, with studies suggesting that it mediates some of the beneficial effects of exercise. Irisin might play a role in 'browning' of white adipocytes, thus increasing energy expenditure. The role of irisin in exercise and energy expenditure in subjects with diabetes mellitus type 2 (DMT2) remains largely unknown. We aimed to investigate the association between circulating irisin and habitual physical activity in subjects with and without DMT2. In this cross-sectional study, 164 Saudi adults: 81 non-DMT2 controls [age: (mean ± SD) 51.6 ± 10.9; BMI: 29.6 ± 4.3 kg/m(2) ] and 83 DMT2 subjects [age: 54.3 ± 10.3 year; BMI: 29.4 ± 4.7 kg/m(2) ] were studied. Anthropometric and fasting serum biochemical data were collected. Circulating irisin was measured using an enzyme-linked immunosorbent assay (ELISA). Frequency intensity time (FIT) index was used to assess the level of habitual physical activity. We observed significantly higher levels of irisin in DMT2 subjects than in controls (P < 0.001). FIT index was positively associated (r = 0.20, P = 0.03) with circulating irisin in controls only. Additionally, irisin levels were significantly higher in tertile 3 (0.75 ± 0.07 μg/mL) than tertile 1 (0.49 ± 0.06 μg/mL) of the FIT index in healthy controls, whilst no such relation with physical activity was observed in DMT2 subjects. This cross-sectional study has shown a weak association of irisin with physical activity levels in healthy controls but not in DMT2 subjects, suggesting the possibility of discordant regulation in the condition of DMT2.

Irisin: a new molecular marker and target in metabolic disorder.

Irisin is a newly discovered exercise-mediated myokine which regulates energy metabolism and has been the subject of much recent research. Irisin plays an important role in metabolic diseases making it a potential new target to combat obesity and its associated disorders, such as T2DM. However, the results of several recent studies investigating the effects of irisin have been controversial. The present review will introduce the discovery of irisin, the role of irisin in metabolic disorders, possible mechanisms, and unanswered questions for future research.

Brown Adipose Tissue and Browning Agents: Irisin and FGF21 in the Development of Obesity in Children and Adolescents.

In the pediatric population, especially in early infancy, the activity of brown adipose tissue (BAT) is the highest. Further in life BAT is more active in individuals with a lower body mass index and one can expect that BAT is protective against childhood obesity. The development of BAT throughout the whole life can be regulated by genetic, endocrine, and environmental factors. Three distinct adipose depots have been identified: white, brown, and beige adipocytes. The process by which BAT can become beige is still unclear and is an area of intensive research. The "browning agents" increase energy expenditure through the production of heat. Numerous factors known as "browning agents" have currently been described. In humans, recent studies justify a notion of a role of novel myokines: irisin and fibroblast growth factor 21 (FGF21) in the metabolism and development of obesity. This review describes a possible role of irisin and FGF21 in the pathogenesis of obesity in children.

Is Irisin an Anticarcinogenic Peptide?

Prostate cancer is the most common type of cancer in males. There has been currently no therapy to cure various types of cancer, and hence, studies aiming to develop cancer treatment are important and have been ongoing. Irisin is a hormone, which regulates body weight and metabolism, including insulin resistance and is thought to have beneficial effects on the properties of antiobesytetic. It is known that obesity is a risk factor in the development of cancer and at the present time, the effects of peptides on cancer thay may reduce obesity have been investigated. This study was carried out to investigate whether there is a role of irisin on human prostate cancer cell viability. In the present study, 0.1, 1, 10 and 100 nM concentrations of irisin were separately applied to human prostate cancer cells with androgen receptor positive (LNCaP) and androgen receptor negative (DU-145, PC3). Effects of irisin on prostate cancer cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. At the end of study, all concentrations of irisin reduced the viability of all three prostate cell types, but only 10 and 100 nM concentrations of the irisin caused a significant decrease (p

Browning of white fat: does irisin play a role in humans?

The discovery of irisin as an exercise-regulated myokine inducing browning of WAT has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes. However, there are inconsistencies regarding the relevance of irisin in humans. The regulation of FNDC5 mRNA expression by exercise and contraction could not be reproduced by a number of human studies using several exercise protocols and in vitro approaches. Furthermore, the nature of FNDC5 fragments and the presence of irisin in humans are questionable and probably contribute to conflicting data obtained with commercially available ELISA kits. Most importantly, the information regarding the concentration of circulating irisin in humans is not clear, as different studies using different kits measure irisin levels in a wide range. Data about the role of irisin in states of human obesity and metabolic diseases are conflicting and, in some cases, changes in irisin levels have been observed; they were only moderate in 10-20%. Independent of the presence and regulation of FNDC5/irisin in humans, the application of recombinant irisin could still represent a therapeutic strategy to fight obesity. However, the current data obtained from human cell models reveal that FNDC5/irisin has no effect on browning of the major WAT depots in humans and is likely to selectively target a small subpopulation of adipocytes, which are located in classical BAT regions, such as the supraclavicular adipose tissue. Thus, other candidates, such as BMP7 or CNPs, seem to be more prominent candidates as inducers of browning in humans.

The Role of Irisin in Gestational Diabetes Mellitus: A Review

Irisin is a newly described myokine that improves insulin resistance via the browning of white adipose tissue. Irisin appears to be secreted in response to exercise, providing a hormonal link between exercise and improved insulin sensitivity. Irisin expression has been demonstrated to increase after acute exercise and cold exposure in animal and human studies. Circulating irisin is decreased in metabolic disease states characterised by insulin resistance, such as type 2 diabetes mellitus, non-alcoholic fatty liver disease, chronic kidney disease and metabolic syndrome. The role of irisin in in normal pregnancy as well as gestational diabetes mellitus is yet to be fully elucidated. To date, there are inconsistent reports regarding the changes in circulating irisin that occur in pregnancy and Gestational Diabetes Mellitus (GDM). Overall, it appears that irisin levels increase with pregnancy, and that the placenta expresses low levels of irisin. There is evidence that irisin levels are decreased in GDM pregnancy. With further research, irisin may prove a future therapeutic target or risk marker for GDM as well as other disease states characterised by insulin resistance.

Irisin, the metabolic syndrome and follistatin in humans

Many important associations have been found between the newly discovered myokine irisin and measures of metabolic disease. However, not much is known regarding the role of irisin in human disease. Two recent reports now identify novel metabolic associations for this molecule in humans.