Irisin: A new potential hormonal target for the treatment of obesity and type 2 diabetes

Sanchís-Gomar, Fabián; Lippi, Giuseppe; Mayero, Sara; Pérez-Quilis, Carme; García-Giménez, José Luis

doi:10.1111/j.1753-0407.2012.00194.x

Cited by 88 publications

(60 citation statements)

References 6 publications

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“…There is a strong rationale in postulating that the gene, FNDC5, encoding the precursor of irisin might be associated, at least partly, with healthy aging (Bostrom et al 2012), based on the beneficial multisystemic effects of this myokine, i.e., browning of white adipocytes (Polyzos et al 2013), reduced risk of obesity (Spiegelman 2013) and related diseases (Sanchis-Gomar et al 2012;Hojlund and Bostrom 2013;Sanchis-Gomar 2013), potential preservation of vascular function and skeletal muscle mass ( (Huh et al 2012;Spiegelman 2013;Bostrom and Fernandez-Real 2014), higher aerobic fitness in cardiac patients (Lecker et al 2012), improved neurogenesis in animal models (Hashemi et al 2013), and also based on the association between irisin levels and higher telomere length in healthy adults (Rana et al 2014). On the other hand, inhibition of another myokine, myostatin, can have irisin-like effects, e.g., "browning" of the white adipose tissue (though AMPK-PGC-1α-irisin pathway) and amelioration of muscle weakness (see Fiuza-Luces et al 2013 for a review).…”

Section: Discussionmentioning

confidence: 99%

“…Some authors have expressed their concerns about the notion that irisin is a real myokine (i.e., being released by contracting muscles) or that this molecule has actual beneficial effects on health (Timmons et al 2012;Erickson 2013;Pekkala et al 2013;Raschke et al 2013). And yet, the bulk of evidence seems to indicate that irisin plays an overall protective role against cardiometabolic disorders (Sanchis-Gomar et al 2012;Eckardt et al 2014) and can be upregulated by muscle exercise . However, despite the overall metabolicprotective effect of irisin, no evidence is available on the potential benefits of irisin to prevent sarcopenia, with recent data showing no differences in irisin levels between subjects with sarcopenia and healthy controls, and also indicating no association between this molecule and skeletal muscle mass index (Choi et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Irisin acts in the white adipose tissue, promoting the acquisition of a brown adipocyte phenotype prone to energy expenditure (Polyzos et al 2013). Accordingly, irisin might play an important role in reducing the risk of obesity (Spiegelman 2013), insulin resistance (Bostrom et al 2012) [included in aged populations (Sanchis-Gomar et al 2014b)], diabetes (Spiegelman 2013), or several related diseases (Sanchis-Gomar et al 2012;Hojlund and Bostrom 2013;Sanchis-Gomar 2013;SanchisGomar and Perez-Quilis 2014). It can also help to preserve vascular function and skeletal muscle mass (Spiegelman 2013;Bostrom and Fernandez-Real 2014).…”

Section: Introductionmentioning

confidence: 99%

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FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

Sanchís-Gomar

Garatachea

et al. 2014

AGE

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Irisin might play an important role in reducing the risk of obesity, insulin resistance, or several related diseases, and high irisin levels may contribute to successful aging. Thus, the irisin precursor (FNDC5) gene is a candidate to influence exceptional longevity (EL), i.e., being a centenarian. It has been recently shown that two single-nucleotide polymorphisms (SNPs) in the FNDC5 gene, rs16835198 and rs726344, are associated with in vivo insulin sensitivity in adults. We determined luciferase gene reporter AGE (2014) 36:9733 DOI 10.1007 Fabian Sanchis-Gomar and Nuria Garatachea contributed equally to this paper activity in the two above-mentioned SNPs and studied genotype distributions among centenarians (n=175, 144 women) and healthy controls (n=347, 142 women) from Spain. We also studied an Italian [79 healthy centenarians (40 women) and 316 healthy controls (156 women)] and a Japanese cohort [742 centenarians (623 women) and 499 healthy controls (356 women)]. The rs726344 SNP had functional significance, as shown by differences in luciferase activity between the constructs of this SNP (all P≤0.05), with the variant A-allele having higher luciferase activity compared with the G-allele (P = 0.04). For the rs16835198 SNP, the variant T-allele tended to show higher luciferase activity compared with the G-allele (P=0.07). However, we found no differences between genotype/allele frequencies of the two SNPs in centenarians versus controls in any cohort, and no significant association (using logistic regression adjusted by sex) between the two SNPs and EL. Further research is needed with different cohorts as well as with additional variants in the FNDC5 gene or in other genes involved in irisin signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

Sanchís-Gomar

Garatachea

et al. 2014

AGE

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“…Irisin is expressed in muscle, and its secretion is particularly stimulated by exercise in mice and humans, thereby it was postulated as able to improve obesity states and glucose homeostasis (Bostrom et al, 2012;CastilloQuan, 2012;Cunha, 2012;Kelly, 2012;Sanchis-Gomar et al, 2012;Villarroya, 2012). In contrast, recent studies have revealed a positive correlation between irisin circulating levels and BMI in humans (Huh et al, 2012;Park et al, in press;Stengel et al, 2012).…”

Section: Discusionmentioning

confidence: 99%

“…Whether irisin is regulated by insulin (Bostrom et al, 2012;Choi et al, 2013;Sanchis-Gomar et al, 2012) acting on fat and muscle cells or by another factor is at present unknown, and further work is necessary to completely understand the fine regulation of irisin secretion and its putative metabolic actions. However, the direct association observed between irisin and insulin together with the inverse correlation between irisin and ghrelin, a circulating orexigenic hormone with opposite pattern that of insulin, could suggest that irisin circulating levels in obesity may represent a compensatory response to the hyperglycemia but acquiring a reduced irisin sensitivity, such as insulin (Polonsky, 2000) and leptin (Montez et al, 2005) resistance, which is commonly present in obesity.…”

Section: Discusionmentioning

confidence: 99%

Longitudinal variation of circulating irisin after an energy restriction‐induced weight loss and following weight regain in obese men and women

Crujeiras

Pardo

Roca-Rivada

et al. 2013

American J Hum Biol

129

117

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Objective: The recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. The objective of this work was to evaluate whether circulating human irisin levels are modulated by body size and changes in adiposity during an energy restriction treatment and the subsequent weight regain.Methods: A group of 94 obese patients (50 men, 44 women; 49.4 6 9.4 years; BMI 35.6 6 4.5 kg/m 2 ) participated in a weight loss program following an 8-week hypocaloric diet (230% energy expenditure) with a weight maintenance follow-up. The patients were evaluated at 0, 8, and 24 weeks after starting treatment. In addition, 48 normal-weight subjects (16 men, 32 women; 35.71 6 8.8 years; BMI 22.9 6 2.2 kg/m 2 ) participated as controls. Plasma irisin, body weight, body composition, and hormones controlling energy homeostasis were measured.Results: Irisin levels were higher in obese subjects (353.1 6 18.6 ng/mL) than in those of normal-weight (198.4 6 7.8 ng/mL; P 0.001) and were also higher in men (340.9 6 20 ng/mL) than in women (267.6 6 12 ng/mL; P < 0.05). Moreover, irisin plasma levels were significantly correlated with high levels of direct and indirect adiposity markers, such as weight, BMI, waist circumference, and fat mass, as measured by bioimpedance, but not with height or leptin levels. Interestingly, irisin levels paralleled body weight reduction after the dietary treatment (week 8) and again returned to the baseline levels at 24 weeks in those patients regaining the lost weight.Conclusions: Irisin strongly reflects body fat mass, suggesting that the irisin circulating levels are conditioned by adiposity level. Am. J. Hum. Biol. 26:198-207, 2014.

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Irisin promotes cardiac progenitor cell‐induced myocardial repair and functional improvement in infarcted heart

Zhao

Wang

Yano³

et al. 2018

Journal Cellular Physiology

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Irisin, a newly identified hormone and cardiokine, is critical for modulating body metabolism. New evidence indicates that irisin protects the heart against myocardial ischemic injury. However, whether irisin enhances cardiac progenitor cell (CPC)-induced cardiac repair remains unknown. This study examines the effect of irisin on CPC-induced cardiac repair when these cells are introduced into the infarcted myocardium. Nkx2.5 CPC stable cells were isolated from mouse embryonic stem cells. Nkx2.5 CPCs (0.5 × 10 ) were reintroduced into the infarcted myocardium using PEGlylated fibrin delivery. The mouse myocardial infarction model was created by permanent ligation of the left anterior descending (LAD) artery. Nkx2.5 CPCs were pretreated with irisin at a concentration of 5 ng/ml in vitro for 24 hr before transplantation. Myocardial functions were evaluated by echocardiographic measurement. Eight weeks after engraftment, Nkx2.5 CPCs improved ventricular function as evident by an increase in ejection fraction and fractional shortening. These findings are concomitant with the suppression of cardiac hypertrophy and attenuation of myocardial interstitial fibrosis. Transplantation of Nkx2.5 CPCs promoted cardiac regeneration and neovascularization, which were increased with the pretreatment of Nkx2.5 CPCs with irisin. Furthermore, irisin treatment promoted myocyte proliferation as indicated by proliferative markers Ki67 and phosphorylated histone 3 and decreased apoptosis. Additionally, irisin resulted in a marked reduction of histone deacetylase 4 and increased p38 acetylation in cultured CPCs. These results indicate that irisin promoted Nkx2.5 CPC-induced cardiac regeneration and functional improvement and that irisin serves as a novel therapeutic approach for stem cells in cardiac repair.

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Irisin: A new potential hormonal target for the treatment of obesity and type 2 diabetes

Cited by 88 publications

References 6 publications

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

FNDC5 (irisin) gene and exceptional longevity: a functional replication study with rs16835198 and rs726344 SNPs

Longitudinal variation of circulating irisin after an energy restriction‐induced weight loss and following weight regain in obese men and women

Irisin promotes cardiac progenitor cell‐induced myocardial repair and functional improvement in infarcted heart

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