Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

Park, Kyung-Hee; Zaichenko, Lesya; Brinkoetter, Mary; Thakkar, Bindiya; Sahin-Efe, Ayse; Joung, Kyoung Eun; Tsoukas, Michael A.; Geladari, Eleni; Huh, Joo Young; Dincer, Fadime; Davis, Cynthia R.; Crowell, Judith A.; Mantzoros, Christos S.

doi:10.1210/jc.2013-2373

Cited by 393 publications

(246 citation statements)

References 36 publications

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“…Additionally, during the peer-review process of the current work, an independent study reported a significant positive correlation between baseline circulating irisin levels and insulin resistance as assessed by HOMA-IR [57].…”

Section: Discussionmentioning

confidence: 87%

“…On the other hand, there has been controversy regarding the stability and range of the commercially available irisin ELISA kits, as this field needs a validated antibody that can quantify levels of FNDC5/irisin protein in plasma [60]. In the current work, the ELISA kit employed was directed against amino acids 32 to 143 which include the extracellular part of the protein according to manufacturer information (Phoenix pharmaceuticals); this kit was the same one employed in previous studies in humans [51,52,57]. In addition, all of the samples in this study were analyzed using the same kit lot number to avoid bias.…”

Section: Discussionmentioning

confidence: 99%

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Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

et al. 2014

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Objective. Weight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain.Materials/Methods. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and were reevaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2).Results. After a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance.Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039).Conclusions. Circulating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

et al. 2014

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“…In addition, decreased serum irisin was found to be associated with the presence, severity, and higher SYNTAX score of coronary artery disease [15, 16]. Serum irisin has also been found to be independently associated with general Framingham risk profile and is a strong positive biomarker for cardiovascular disease risk within 10 years [25]. Besides that, increased circulating irisin levels were also demonstrated to be associated with MACE in coronary artery disease patients after percutaneous coronary interventions.…”

Section: Discussionmentioning

confidence: 99%

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients

Shen

Gao

Bei

et al. 2017

Cell Physiol Biochem

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Background/Aims: Irisin is a peptide hormone cleaved from a plasma membrane protein fibronectin type III domain containing protein 5 (FNDC5). Emerging studies have indicated association between serum irisin and many major chronic diseases including cardiovascular diseases. However, the role of serum irisin as a predictor for mortality risk in acute heart failure (AHF) patients is not clear. Methods: AHF patients were enrolled and serum was collected at the admission and all patients were followed up for 1 year. Enzyme-linked immunosorbent assay was used to measure serum irisin levels. To explore predictors for AHF mortality, the univariate and multivariate logistic regression analysis, and receiver-operator characteristic (ROC) curve analysis were used. To determine the role of serum irisin levels in predicting survival, Kaplan-Meier survival analysis was used. Results: In this study, 161 AHF patients were enrolled and serum irisin level was found to be significantly higher in patients deceased in 1-year follow-up. The univariate logistic regression analysis identified 18 variables associated with all-cause mortality in AHF patients, while the multivariate logistic regression analysis identified 2 variables namely blood urea nitrogen and serum irisin. ROC curve analysis indicated that blood urea nitrogen and the most commonly used biomarker, NT-pro-BNP, displayed poor prognostic value for AHF (AUCs ≤ 0.700) compared to serum irisin (AUC = 0.753). Kaplan-Meier survival analysis demonstrated that AHF patients with higher serum irisin had significantly higher mortality (P<0.001). Conclusion: Collectively, our study identified serum irisin as a predictive biomarker for 1-year all-cause mortality in AHF patients though large multicenter studies are highly needed.

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“…Although several studies have shown irisin to be positively associated with insulin resistance (Park et al. 2013; Crujeiras et al. 2014; Ebert et al.…”

Section: Introductionmentioning

confidence: 99%

Increased FNDC5 is associated with insulin resistance in high fat-fed mice

et al. 2017

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FNDC5/irisin, has recently been identified as a novel protein that stimulates the “browning” of white adipose by inducing thermogenesis via increased uncoupling protein 1 (UCP1). We tested the hypothesis that high fat diet‐induced prediabetic mice would exhibit increased FNDC5 and this effect would be attenuated by chronic exercise. C57BL/6 mice were randomized into three groups for the 4 week intervention: Standard diet (Std, n = 12), High fat diet (HF, n = 14), or High fat diet and free access to a running wheel (HFEX, n = 14). Body weight, glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA‐IR) were greater in HF compared to Std and HFEX after the 4 week intervention. In support of our hypothesis, FNDC5 was higher in HF in both skeletal muscle and adipose compared to Std and was lower in adipose only in HFEX compared to HF mice. Following the same pattern, PGC‐1α was significantly higher in HF compared to Std in skeletal muscle and significantly lower in HFEX compared to HF in adipose. UCP1 was significantly lower in HFEX versus Std (in skeletal muscle) and versus HF (in adipose). HOMA‐IR was significantly correlated with FNDC5 protein levels in adipose. Increased FNDC5 in adipose and skeletal muscle may be a compensatory mechanism to offset high fat diet‐induced weight gain and insulin resistance by increasing energy expenditure.

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Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

Abstract: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.

Cited by 393 publications

References 36 publications

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

Serum Irisin Predicts Mortality Risk in Acute Heart Failure Patients

Increased FNDC5 is associated with insulin resistance in high fat-fed mice

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