Irisin Expression Research Articles

Effect of sleeve gastrectomy on the expression of meteorin-like (METRNL) and Irisin (FNDC5) in muscle and brown adipose tissue and its impact on uncoupling proteins in diet-induced obesity rats.

Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves metabolic homeostasis by modulating energy expenditure and enhancing thermogenesis through increasing the expression level of meteorin-like protein (METRNL) and fibronectin type III domain-containing protein 5 (FNDC5/Irisin) through uncoupling proteins 1/2/3 (UCP1, UCP2, and UCP3). To study the effect of SG on the levels of proteins involved in thermogenesis process. Laboratory rats at Kuwait University. Male Sprague-Dawley rats, aged 4 to 5 weeks, were divided into 2 groups, control (n = 11) and diet-induced obesity (DIO) (n = 22). The control group was fed regular rat chow ad libitum, whereas the DIO group was fed cafeteria diet "high-fat/carbohydrate diet" ad libitum. At 21 weeks, rats in the DIO group that weighed 20% more than the control group animals underwent surgery. These rats were randomly subdivided into Sham and SG operation groups. Gene expression was evaluated, and enzyme-linked immunosorbent assays were employed to assess the changes in gene and protein levels in tissue and circulation. The protein expression data revealed an increase in METRNL levels in the muscles and white adipose tissue of SG animals. METRNL level in circulation in SG animals was reduced compared with control and Sham rats. The level of Irisin increased in the muscle of SG animals compared with the control and Sham group animals; however, a decrease in Irisin level was observed in the white adipose tissue and brown adipose tissue of SG animals compared with controls. Gene expression analysis revealed decreased METRNL levels in muscle tissues in the SG group compared with the control group animals. Increased expression of FNDC5 (Irisin), UCP2, and UCP3 in the muscle tissue of SG animals was also observed. Furthermore, the levels of UCP1, UCP2, UCP3, and METRNL in the brown adipose tissue of SG animals were upregulated. No significant alteration in the gene expression of Irisin was observed in brown adipose tissue. Sleeve gastrectomy induces weight loss through complex mechanisms that may include browning of fat.

Aerobic exercise alleviates oxidative stress-induced apoptosis in kidneys of myocardial infarction mice by inhibiting ALCAT1 and activating FNDC5/Irisin signaling pathway

Aerobic exercise involves in ameliorating kidney injury, but the underlying mechanisms are not fully clarified. In this study, we elucidated the potential mechanisms of aerobic exercise in ameliorating kidney injury following myocardial infarction (MI). In vivo, wildtype and alcat1 knockout mice were used to establish the MI model, and subjected to six-week moderate-intensity aerobic exercise. In vitro, Normal Rat Kidney (NRK) cells treated with H2O2 and recombinant human Irisin (rhIrisin) were used for exploring potential mechanisms. Our results showed that Irisin expression was up-regulated by aerobic exercise in kidneys after MI, while ALCAT1 was reduced. In alcat1 knockout mice, we found that ALCAT1 involved in the progressions of oxidative stress and apoptosis in impaired kidney tissues of MI mice, but aerobic exercise reversed these changes. Furthermore, in vitro, we observed that Irisin inhibited both H2O2-treatment or overexpression of alcat1-induced oxidative stress and apoptosis in NRK cells, partially via AMPK-Sirt1-PGC-1α pathway. These findings reveal that aerobic exercise participates in alleviating the levels of oxidative stress and apoptosis in impaired kidney tissues following MI, partially via activating FNDC5/Irisin-AMPK-Sirt1-PGC-1α signaling pathway and inhibiting ALCAT1 expression.

Review of Research on the Role of Irisin in Tumors.

Irisin is a newly discovered exercise-induced cytokine, produced by the proteolytic hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Irisin is widely distributed in the human body and is involved in the browning of white adipose tissue, improving insulin resistance, improving cognitive function, and regulating bone metabolism. Recent studies have shown that irisin concentration is elevated in a variety of tumor tissues as compared with that in normal tissues. However, irisin has different effects on the proliferation and apoptosis of tumor cells in breast cancer, lung cancer, and liver cancer through various mechanisms. Irisin plays an important role in the occurrence, development, and metastasis of different tumors, suggesting that irisin can be used as a potential target for tumor diagnosis and treatment. Therefore, studying the expression and function of irisin in tumors may be of great significance for the prevention and treatment of tumors. This article reviews the research progress on the role of irisin in tumors.

Auricular acupuncture induces FNDC5/irisin and attenuates obese inflammation in mice.

To investigate whether auricular acupuncture (AA) attenuates bodyweight and obese inflammation through the release of irisin from muscle tissue in mice. Sixty 4-week-old mice were fed a high fat diet (HFD) for 4 weeks. These animals were divided into six groups that remained untreated (HFD) or underwent electrical AA (HFD+EAA), sham EAA (HFD+SEAA), adrenalectomy (HFD+AD), adrenalectomy and EAA (HFD+AD+EAA), or adrenalectomy and injection of recombinant lentivirus expressing fibronectin type III domain-containing protein 5 (rFNDC) (HFD+AD+rFNDC) in the ninth week. The EAA and SEAA were performed at two traditional auricular acupuncture points daily for 4 weeks. An additional 10 mice fed a control diet were included as a normal control (NC) group. At the end of the study, norepinephrine (NE) in the serum, tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β) in the serum and white adipose tissue, irisin in the serum and muscle, uncoupling protein-1 (UCP-1) in the brown adipose tissue (BAT), and FNDC5 in the muscle, were analysed. The AD+EAA group exhibited better control of bodyweight and inflammation compared with the AD+SEAA and untreated HFD model groups (P<0.05), especially regarding the increased expression of NE, FNDC5, irisin and UCP-1 (P<0.05). After adrenalectomy, mice receiving EAA had less NE, FNDC5, irisin and UCP-1 as well as greater expression of inflammatory cytokines and bodyweight. However, lentiviral overexpression of rFNDC successfully reversed this situation in the AD mice and mimicked the effects of EAA on bodyweight, inflammation and expression of FNDC5, irisin and UCP-1, although it did not impact NE. EAA promoted NE release from the adrenal gland leading to further expression of FNDC5, irisin and UCP-1, which contributed to weight management and inflammatory inhibition.

Blunted circulating irisin in adults with type 1 diabetes during aerobic exercise in a hot environment: a pilot study

Irisin is a novel myokine associated with increased metabolism, which may be upregulated in type 1 diabetes (T1D) during exercise-heat stress. We therefore assessed serum irisin production in young adults with and without T1D during incremental exercise in dry-heat (35 °C). The change in irisin during exercise was lower in individuals with compared with without T1D (-1.79 (SEM 25.68) vs. 59.74 (SEM 79.63) pg/mL; p = 0.024), indicating that irisin expression during exercise-heat stress is blunted in T1D. Novelty We show that, when assessed in young adults with and without T1D during exercise-heat stress, serum irisin production is blunted in T1D.

Irisin ameliorates the postoperative depressive-like behavior by reducing the surface expression of epidermal growth factor receptor in mice

Postoperative depression is a serious problem with under-optimized treatment. Our previous result demonstrated that single dose of propofol exposure in mice could cause depressive-like behavior. In the present study, we explored the possible preventive strategy that could ameliorate the depressive-like behavior in mice. Irisin was used for co-treatment with propofol in mice to test whether irisin could prevent the depressive-like behavior in mice. We found irisin could significantly reduce the immobility time in tail suspension and forced swimming tests in mice with propofol. We also found irisin was able to protect neurons against high concentration propofol treatment induced cell death in cultures. Meanwhile, irisin could significantly inhibit the increase of cytokines in astrocyte cultures exposed to propofol. These in vitro results suggested that interaction between astrocyte and neuron may be involved in the action mechanism that irisin prevented the mice from developing of depressive-like behavior. Last, we revealed that propofol caused increased surface expression of epidermal growth factor receptor (EGFR) but irisin could reduce the expression level of EGFR on cell surface.

Irisin Improves Autophagy of Aged Hepatocytes via Increasing Telomerase Activity in Liver Injury.

An aged liver has decreased reparative capacity during ischemia-reperfusion (IR) injury. A recent study showed that plasma irisin levels predict telomere length in healthy adults. The aim of the present study is to clarify the role of irisin, telomerase activity, and autophagy during hepatic IR in the elderly. To study this, hepatic IR was established in 22-month- and 3-month-old rats and primary hepatocytes were isolated. The results showed that the old rats exhibited more serious liver injury and lower levels of irisin expression, telomerase activity, autophagy ability, and mitochondrial function than young rats during hepatic IR. Irisin activated autophagy and improved mitochondrial function via increasing telomerase activity in aged hepatocytes. Inhibition of telomerase activity by BIBP1532 abolished the protective role of irisin in hepatocytes during hypoxia and reoxygenation. Additionally, this study proved irisin increased the telomerase activity via inhibition of the phosphorylation of JNK during hepatic IR. Administration of exogenous irisin significantly mitigated the inflammation, oxidative stress, apoptosis, and liver injury in an old rat model of hepatic IR. In conclusion, irisin improves autophagy of aged hepatocytes via increasing telomerase activity in hepatic IR. Irisin exhibits conspicuous benefits in increasing reparative capacity of an aged liver during hepatic IR.

Irisin and troponin I expression in dialysis patients submitted to remote ischemic preconditioning: a pilot study.

ABSTRACTBackground:Renal replacement therapy continues to be related to high hospitalization rates and poor quality of life. All-cause morbidity and mortality in renal replacement therapy in greater than 20% per year, being 44 times greater when diabetes is present, and over 10 times that of the general population. Regardless of treatment, the 5-year survival is 40%, surpassing many types of cancers. Irisin is a hormone that converts white adipose tissue into beige adipose tissue, aggregating positive effects like fat mass control, glucose tolerance, insulin resistance, prevention of muscle loss, and reduction in systemic inflammation.Objectives:To determine the serum levels of troponin I in hemodialysis patients submitted to remote ischemic preconditioning (RIPC) associated with irisin expression.Methods: This was a prospective, randomized, double-blind clinical trial with patients with chronic kidney disease submitted to hemodialysis for a 6-month period. Troponin I, IL-6, urea, TNF-α, and creatinine levels were determined from blood samples. The expressions of irisin, thioredoxin, Nf-kb, GPX4, selenoprotein and GADPH were also evaluated by RT-PCR.Results:Samples from 14 hypertensive patients were analyzed, 9 (64.3%) of whom were type 2 diabetics, aged 44-64 years, and 50% of each sex. The difference between pre- and post-intervention levels of troponin I was not significant. No differences were verified between the RIPC and control groups, except for IL-6, although a significant correlation was observed between irisin and troponin I.Conclusion:Remote ischemic preconditioning did not modify irisin or troponin I expression, independent of the time of collection.

Grape pomace extract supplementation activates FNDC5/irisin in muscle and promotes white adipose browning in rats fed a high-fat diet.

Irisin is a myokine regulated by peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) in the exercising skeletal muscle and released into the bloodstream after cleavage of FNDC5. Circulating irisin can up-regulate UCP-1 expression in white adipose tissue (WAT) promoting the formation of brown-like adipocytes. The aim of this study was to evaluate if supplementation with a grape pomace extract (GPE) could activate the FNDC5/irisin pathway via PGC-1α in rats fed a high fat diet (HFD). For this purpose we characterized the activation of: i. the FNDC5/irisin pathway and AMPK in skeletal muscle and ii. proteins involved in the formation of brown-like cells in epididymal WAT (eWAT). Consumption of the GPE activated the FNDC5/irisin pathway, increased AMPK phosphorylation in skeletal muscle and enhanced irisin plasma levels. In eWAT, the GPE increased the level of proteins involved in WAT browning, i.e. PGC-1α, PPARγ, PRDM16 and UCP-1. The GPE also prevented HFD-induced adipocyte hypertrophy and systemic insulin resistance. Consistently, in L6 myotubes, (-)-epicatechin (EC), a flavonoid abundant in the GPE, prevented palmitate-mediated downregulation of FNDC5/irisin protein expression and secretion, in part via PGC-1α activation. Consumption of the GPE, a winemaking residue rich in bioactive compounds, could be a beneficial strategy to counteract the adverse effects of Western style diets through the promotion of WAT browning.

Serum Irisin Predicts Posthepatectomy Complications in Patients with Hepatocellular Carcinoma.

Background Hepatectomy remains one of the most effective treatments for patients with hepatocellular carcinoma (HCC); however, it can lead to serious complications. Irisin, a key regulator of energy metabolism, is secreted into the circulation by shedding of the extracellular portion of the fibronectin type III domain-containing 5 (FNDC5). We have shown that irisin administration alleviates liver ischemia-reperfusion injury in mice. However, the role of preoperative irisin levels in HCC patients who underwent hepatectomy remained unknown. The purpose of this study was to determine how irisin expression changes in HCC and to explore the relationship between preoperative serum irisin levels and complications after hepatectomy. Methods FNDC5/irisin expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. A total of 219 participants, including 102 healthy controls and 117 HCC patients, were recruited in this study. All HCC patients underwent hepatectomy at the First Affiliated Hospital of the Xi'an Jiaotong University. Preoperative serum irisin levels were measured by ELISA. Postoperative complications were assessed using the comprehensive complication index (CCI) score. The Pearson rank correlation coefficient was computed to assess the correlation between preoperative serum irisin levels and postoperative CCI scores. Results In TCGA dataset, FNDC5/irisin expression was downregulated in HCC tissues (P < 0.001). Similarly, serum irisin levels were decreased in HCC patients (P < 0.001). Low preoperative serum irisin levels were significantly correlated with high CCI scores after hepatectomy. Conclusions Irisin may be a novel serum biomarker in the diagnosis of HCC and a predictor of complications after hepatectomy.

Irisin is expressed by undifferentiated spermatogonia and modulates gene expression in organotypic primate testis cultures

The molecular mechanisms regulating undifferentiated spermatogonial cell proliferation and differentiation are still not fully understood. Irisin is an exercise-induced hormone, which is a cleaved and secreted fragment of the fibronectin type III repeat containing 5 (FNDC5) transmembrane protein. Recent studies have demonstrated the role of irisin in cell proliferation and differentiation in various tissues. However, testicular irisin expression and its potential action have not been analyzed. Here, we demonstrate expression of irisin in undifferentiated spermatogonia of primates and in the tree shrew, a bridging species between primates and insectivores. Rhesus monkeys are seasonal breeders with annual phases of high and low testicular activity and germ cell proliferation. Interestingly, expression of both FNDC5 mRNA and irisin is altered between breeding (high spermatogenesis) and nonbreeding seasons (low spermatogenesis). Organotypic testis culture in the presence of irisin increased the expression levels of the Sertoli cell (GDNF) and spermatogonial transcripts Kruppel-like factor 4 (KLF4), Inhibitor of differentiation 4 (ID4), Cluster of differentiation 117 (cKIT), and SALL4, compared to untreated controls, while irisin suppressed its own FNDC5 mRNA. Our data suggest that irisin is a novel endocrine factor involved in the regulation of spermatogonial activities in the testes of primates.

철인3종 경기 코스에 따른 경기 직후, 회복 시 혈중 아이리신 호르몬 농도의 변화

Purpose: The purpose of this study is to provide scientific evidence on the effects of long-term, high-intensity aerobic exercise on induction of irisin expression and its timing by measuring irisin levels during recovery and immediately after triathlon races according to course types.BR Method: In this study, 10 male amateur triathlon athletes aged between 30 and 49 years were recruited. Blood irisin levels were drawn 4 times at rest, immediately after the race, and during recovery (3 and 6 days after the race) in those who participated in the Olympic course(1.5km swimming, 40km cycling, and 10km running) and in the O2 course (3km swimming, 80km cycling, and 20km running) one month after. Using SPSS/PC+Ver.21.0K, the mean ± standard error values for all dependent variables were calculated. To determine the differences in irisin levels according to course types, two-way repeated ANOVA was performed according to course types and irisin measurement periods. If an interaction was observed, one-way ANOVA and paired t-test were performed to determine the simple main effects on the independent variable. Statistical significance was defined as α=0.05.BR Results: For the Olympic course, there was a significant increase in irisin levels from before the race to 3 days after the race (p0.01), immediately after the race to 3 days after the race (p0.01), and immediately after the race to 6 days after the race p(0.01). For the O2 course, irisin levels significantly increased from before the race to 3 days after the race (p0.01), before the race to 6 days after the race (p0.01), immediately after the race to 6 days after the race p(0.01), and 3 days after the race to 6 days after the race (p0.01). There was a significant difference in irisin levels 6 days after the race between the Olympic and O2 courses (p0.01).BR Conclusion: High-intensity aerobic exercise increases blood irisin levels. Furthermore, longer durations of exercise lead to higher levels of irisin for a longer period of time. This study demonstrates that long-term high-intensity aerobic exercise contributes to the increase of blood irisin levels.

Expression of Irisin/FNDC5 in Cancer Cells and Stromal Fibroblasts of Non-small Cell Lung Cancer.

Background: Recent in vitro studies have indicated that irisin inhibits proliferation, migration and epithelial-mesenchymal transition. Irisin expression has not been studied in tumour tissues of non-small cell lung cancer (NSCLC) patients yet. The aim of the study was to determine the irisin expression in NSCLCs in comparison to the clinicopathological factors and expression of TTF-1, p63 and Ki-67. Material and methods: Tissue microarrays with 729 NSCLC and 140 non-malignant lung tissue (NMLT) were used to perform immunohistochemical reactions. Laser Capture Microdissection (LCM) was used to collect cancer and stromal cells from NSCLCs. FNDC5 expression was tested for LCM samples, 75 NSCLCs and 25 NMLTs with the RT-PCR technique. Western-blot, immunofluorescence reaction and RT-PCR assays were performed on lung cancer cell lines. Results: Irisin expression was observed in NSCLC cancer cells and stromal fibroblasts. In cancer cells, irisin expression was decreased in higher grades (G) of malignancy, tumour size (T) and according to lymph node metastasis. In stromal cells, irisin expression was increased in higher G and advanced T. A shorter overall survival was observed in patients with higher irisin expression in NSCLC stromal cells. Conclusions: Irisin expression in stromal fibroblasts may influence cancer cell proliferation and may be a prognostic factor for survival in NSCLC.

Maternal serum, placental, and umbilical venous blood irisin levels in intrahepatic cholestasis of pregnancy

Objective To explore the changes of serum, umbilical vein, placental irisin level, and the correlation between irisin level and relevant indicators in pregnant women with intrahepatic cholestasis of pregnancy (ICP), so as to provide a new perspective for in-depth studies on the causes and treatment of ICP. Methods This cross-sectional case–control study method, the serum, umbilical venous blood irisin, liver, kidney function, lipid metabolism, and other indicators of 108 normal pregnant women, 64 patients with mild ICP, and 39 patients with severe ICP were compared, and the changes in the levels of oxidative stress and irisin were observed by dihydroethidium staining and immunohistochemistry. Results The level of placental oxidative stress in severe ICP group and mild ICP group was significantly higher than that in normal pregnant women group, and the mild ICP group was significantly higher than that in severe ICP group (p < .05); the concentration of irisin in umbilical vein was significantly lower than that in peripheral blood; the serum irisin of normal pregnant women (918.51 ± 159.90 pg/ml) was significantly lower than that of pregnant women with mild ICP (1030.05 ± 137.98 pg/ml) and pregnant women with severe ICP (1094.34 ± 154.35 pg/ml). The concentration of irisin in umbilical vein blood of pregnant women with severe ICP (858.78 ± 97.42 pg/ml) was significantly higher than that of normal pregnant women (595.33 ± 162.70 pg/ml) and those with mild ICP (648.82 ± 164.81 pg/ml) (p < .05). Irisin was expressed in placental tissues of normal pregnant women group, mild ICP group and severe ICP group, and the differences were statistically significant in expression intensity of the three groups (χ 2 = 19.959, p < .05). The irisin expression intensity in the ICP group was higher than that in the control group, and the irisin expression intensity in the ICP group was higher than that in the ICP group (β = 0.292; t = 3.063; p < .05). At the best cutoff level of 989.168 pg/ml, irisin accurately predicted ICP [AUC = 0.622 (95%CI 0.543–0.701, p < .05)] with sensitivity and specificity rates of 60.9 and 40.1%, respectively. Conclusion Irisin can reduce the level of oxidative stress and improve lipid metabolism in ICP patients during the pathophysiological process of ICP, and it is possible to become a new auxiliary factor of ICP diagnosis and indexing.

Role of irisin in androgen-deficient muscle wasting and osteopenia in mice.

Androgen deficiency plays a crucial role in the pathogenesis of male osteoporosis and sarcopenia. Myokines have recently been identified as humoral factors that are involved in the interactions between muscle and bone; however, the influence of androgen deficiency on these interactions remains unclear. Therefore, we herein investigated the roles of humoral factors linking muscle to bone using orchidectomized mice with sarcopenia and osteopenia. Orchidectomy (ORX) significantly reduced muscle mass, grip strength, and trabecular bone mineral density (BMD) in mice. Among the myokines examined, ORX only significantly reduced fibronectin type III domain-containing 5 (Fndc5) mRNA levels in both the soleus and gastrocnemius muscles of mice. In simple regression analyses, Fndc5 mRNA levels in the soleus muscle positively correlated with trabecular BMD, but not cortical BMD. The administration of irisin, a product of Fndc5, significantly protected against the decrease induced in trabecular BMD, but not muscle mass, by androgen deficiency in mice. In conclusion, the present results demonstrated that androgen deficiency decreases the expression of irisin in the skeletal muscle of mice. Irisin may be involved in muscle/bone relationships negatively affected by androgen deficiency.

Irisin Exerts Inhibitory Effect on Adipogenesis Through Regulation of Wnt Signaling.

Irisin is an exercise-induced myokine known to induce adipocyte browning through induction of uncoupling protein 1. Recent studies have reported that irisin is also an adipokine. However, there is limiting evidence on the role of endogenous irisin from adipocytes. In this study we aim to elucidate the expression and secretion pattern of irisin during adipocyte differentiation and the role of endogenous and exogenous irisin on the adipogenic process. As such, recombinant irisin, plasmid expressing FNDC5 and small interfering RNA were utilized. Our results show that the gene expression of irisin precursor FNDC5 and irisin secretion increases at the early stage of adipogenesis. Both recombinant irisin treated cells and FNDC5-overexpressed cells resulted in inhibition of adipogenesis evidenced by downregulated C/EBPα, PPARγ, and FABP4 expression and reduced lipid accumulation. Further data showed that the inhibitory effect of irisin on adipogenesis is mediated though potentiation of Wnt expression, which is known to determine the fate of mesenchymal stem cells and regulate adipogenesis. Conversely, FNDC5 knockdown cells showed downregulated Wnt expression, but failed to further induce adipogenesis. This study suggests that both exogenous and endogenous irisin is able to inhibit adipogenesis and that activation of Wnt and subsequent repression of transcription factors is partly involved in this process. This provides a novel insight on the local effect of irisin on adipocytes and additional benefit to protect against obesity-related metabolic disorders.

Effect of electroacupuncture combined with treadmill exercise on body weight and expression of PGC-1α， Irisin and AMPK in skeletal muscle of diet-induced obesity rats

To investigate the effect of electroacupuncture (EA) plus treadmill exercise on the expression of peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α), Irisin, AMP-activated protein kinase (AMPK) in skeletal muscle of diet-induced obesity (DIO) rats, so as to explore its mechanism underlying body reduction promotion. Forty-two male SD rats were divided into normal diet (control, n＝10), high fat diet (model), EA, treadmill exercise and EA plus treadmill exercise (combination) groups (n＝8 in each of the latter 4 groups). The obesity model was established by feeding the rats with high fat diet. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Tianshu" (ST25) for 30 min, 5 times per week for a total of 8 weeks. Rats of the treadmill exercise group were forced to perform exercise on a treadmill (16 m/min) for 30 min, 5 times per week for a total of 8 weeks. Rats in the combination group received the above-mentioned two methods. During the treatment, rats in the control group were fed with normal fodder, rats in other groups were fed with high fat fodder, and their body weight was measured once a week. The expression levels of PGC-1α， fibronectin type Ⅲ domain containing 5 (FNDC5), AMPK mRNA and protein of skeletal muscle were measured by quantitative real-time PCR and Western blot，respectively. After modeling, the body weight was significantly increased (P<0.05), and the expression levels of PGC-1α and FNDC5 mRNA and protein, AMPK mRNA and phosphorylated AMPK (p-AMPK) protein in the skeletal muscle were considerably decreased in the model group relevant to the control group (P<0.05). Following the treatment, the body weight was significantly down-regulated, while the expression levels of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA and p-AMPK protein were obviously up-regulated in the EA, treadmill exercise and combination groups relevant to the model group (P<0.05). The therapeutic effect of EA plus treadmill exercise was significantly superior to those of both simple EA and simple treadmill exercise in down-regulating the body weight, as well as in up-regulating the expression of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA, and p-AMPK protein (P<0.05). Both EA and treadmill exercise can significantly increase the expression of PGC-1α， FNDC5 and p-AMPK in skeletal muscle of DIO rats, suggesting their efficacy in restoring fatty acid oxidation in skeletal muscle cells and improving mitochondrial function, which may contribute to their function in body reduction. The therapeutic effect of EA plus treadmill exercise is better than that of simple EA and simple treadmill exercise.

Comparison of the Effects of Two Different Intensities of Combined Training on Irisin, Betatrophin, and Insulin Levels in Women with Type 2 Diabetes

Background: Betatrophin is a β-cell proliferation marker produced as a result of irisin expression. It is regarded as a therapeutic indicator of diabetes due to elevated insulin secretion. Objectives: The purpose of this study was to compare the effects of 2 different intensities of combined training on the levels of irisin, betatrophin, and insulin in women with type 2 diabetes. Methods: In this study, 26 female patients with type 2 diabetes were divided into 3 groups of combined high-intensity training, combined moderate-intensity training, and control. The training groups participated in combined training at high or moderate intensities for 8 weeks. The variance analysis test and the Duncan post-hoc test were applied to analyze the data (P > 0.05). Results: Combined training at 2 intensities of moderate and vigorous led to a rise in the levels of irisin, betatrophin, and insulin. Exercise intensity was a determining factor for these elevated levels insofar as combined high-intensity training resulted in higher levels of these hormones than combined moderate-intensity training. Conclusions: It appears that participating in relatively high-intensity training programs may be beneficial for diabetic patients inasmuch as they increase the levels of irisin, betatrophin, and then, insulin.

Metformin-induced autophagy and irisin improves INS-1 cell function and survival in high-glucose environment via AMPK/SIRT1/PGC-1α signal pathway.

In order to explore the protective function of metformin on pancreatic β cells to alleviate insulin resistance and underlying mechanisms, INS‐1 cells were cultured into normal control (N), high glucose (H), high glucose and metformin (H + Met), high glucose and chloroquine (H + CQ), and high glucose and Ex527 (H + Ex527) groups, respectively. Upon 24‐hr cultivation, the proliferation and glucose‐stimulated insulin secretion (GSIS) of INS‐1 cells were determined, and the expression of irisin and other proteins associated with AMPK/SIRT1/PGC‐1α signal pathway, autophagy, and apoptosis was evaluated. Compared with the N group, the cells from the H group revealed lower proliferation, GSIS, and expression of irisin and proteins associated with AMPK/SIRT1/PGC‐1α signal pathway and autophagy, but higher expression of proteins associated with apoptosis; in contrast, metformin could significantly rescue lower cell proliferation, GSIS, and expression of proteins associated with AMPK/SIRT1/PGC‐1α signal pathway and autophagy, as well as irisin, and suppress apoptosis in high‐glucose environment. Meanwhile, autophagy inhibitor CQ and SIRT1 inhibitor Ex527 can block above functions of metformin. Therefore, metformin can promote INS‐1 cell proliferation, enhance GSIS, and suppress apoptosis by activating AMPK/SIRT1/PGC‐1α signal pathway, up‐regulating irisin expression, and inducing autophagy in INS‐1 cells in high‐glucose environment.

EXPRESSION OF IRISIN AND ITS RELATION WITH ANTHROPOMETRIC AND BIOCHEMICAL PARAMETERS IN DIABETES MELLITUS TYPE II PATIENTS

AimTo evaluate the gene expression of irisin in patients with type 2 diabetes mellitus (DM2) and its possible involvement in the metabolic changes and obesity in this pathophysiological situation.MethodsPatients anthropometric data were obtained, as well as samples of blood were collected in the clinic of specialties from Faculty of Medicine of ABC. A list of healthy individuals CT (n=14) and DM2 patients (n=16) diagnosed for less than 10 years was obtained. The criteria for the diagnosis of DM2 were the one used by the American Diabetes Association (ADA). Volunteers filled in terms of consent, and all of them were greater than or equal to 21 years old. After collection, it was evaluated complete hemogram and biochemical parameters: glucose and glycated hemoglobin (A1C). The expression of molecular biomarker irisin in peripheral blood leukocytes was performed by RT‐qPCR technique. Results were expressed as mean ± standard deviation (SD) and analyzed by the program GraphPad Prism® 6.0, using the Student's t‐test and Mann‐Whitney test. As for the analyzes of correlation, it was done the Spearman correlation test. The significance level was 5% (descriptive value *p&lt;0.05).ResultsThe mean age of the patients studied was 51±15 years for the CT group (n=14) and 64±10 years for the DM2 (n=16). As for the biochemical parameters, the following results were obtained: glucose (CT 92±13, n=14 DM2 versus 143±40 mg/dL, n=16 *p&lt;0.05); A1C (CT 5.6±0.5, n=14 DM2 versus 7.1±1.6%, n=16 *p&lt;0.05); irisin gene expression in peripheral blood was obtained by the formula 2^‐ΔCT and values found in CT group were 8.506e‐006±1.412e‐005, n=6. The ones found in DM2 group were 0.02288± 0.08050 n=14, p=0.06. The correlation test between the expression of irisin versus Body Mass Index (BMI) in DM2 was r=0.5221, p=0.06. There was no correlation between the glucose levels and A1C with irisin expression.ConclusionDespite the preliminary findings, the data showed a tendency toward a positive correlation between the expression of irisin and BMI in diabetic patients. These data suggest that irisin is associated to possible changes in adiposity which happen in obesity associated to DM2.Support or Funding InformationFinancial Support: CAPES, CNPq.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.