scholarly journals Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Mar Quiñones ◽  
Cintia Folgueira ◽  
Estrella Sánchez-Rebordelo ◽  
Omar Al-Massadi

Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5) that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO) rats and leptin-deficient (ob/ob) mice), as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance.

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1602
Author(s):  
Guangsu Zhu ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
Wei Chen ◽  
Gang Wang

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut–brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Pallav Sengupta ◽  
Sulagna Dutta ◽  
Ivan Rolland Karkada ◽  
Roland Eghoghosoa Akhigbe ◽  
Suresh V. Chinni

Irisin is a novel skeletal muscle- and adipose tissue-secreted peptide. It is conventionally regarded as an adipomyokine and is a cleaved fragment of Fibronectin type III domain-containing protein 5 (FNDC5). It is involved in the browning of white adipose tissue, glucose tolerance, and reversing of metabolic disruptions. Fertility is closely linked to energy metabolism and the endocrine function of the adipose tissue. Moreover, there is established association between obesity and male infertility. Irisin bears strong therapeutic promise in obesity and its associated disorders, as well as shown to improve male reproductive functions. Thus, irisin is a molecule of great interest in exploring the amelioration of metabolic syndrome or obesity-induced male infertility. In this review we aim to enumerate the most significant aspects of irisin actions and discuss its involvement in energy homeostasis and male reproduction. Though current and future research on irisin is very promiscuous, a number of clarifications are still needed to reveal its full potential as a significant medicinal target in several human diseases including male infertility.


2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Junzhou Zhao ◽  
Linlan Qiao ◽  
Jian Dong ◽  
Rongqian Wu

Oxidative stress is a crucial factor in the development of various liver diseases. Irisin, a metabolic hormone discovered in 2012, is mainly produced by proteolytic cleavage of fibronectin type III domain containing 5 (FNDC5) in skeletal muscles. Irisin is induced by physical exercise, and a rapidly growing body of literature suggests that irisin is, at least partially, responsible for the beneficial effects of regular exercise. The major biological function of irisin is believed to be involved in the maintenance of metabolic homeostasis. However, recent studies have suggested the therapeutic potential of irisin against a variety of liver diseases involving its antioxidative function. In this review, we aim to summarize the accumulating evidence demonstrating the antioxidative effects of irisin in liver diseases, with an emphasis on the current understanding of the potential molecular mechanisms.


2018 ◽  
Vol 48 (1) ◽  
pp. 227-236 ◽  
Author(s):  
Bing Zhou ◽  
Li Ling ◽  
Feng Zhang ◽  
Tong-Yan Liu ◽  
Hong Zhou ◽  
...  

Background/Aims: Fibronectin type III domain-containing 5 (FNDC5) protein is involved in the beneficial effects of exercise on metabolism. FNDC5 attenuates hepatic steatosis induced by high fat diet (HFD). Here, we examined the effects of FNDC5 on liver fibrosis and underline mechanisms. Methods: Experiments were carried out on wild-type and FNDC5-/- mice, primary mouse hepatic stellate cells (HSCs) and human hepatic stellate cell line (LX-2). The mice were fed with HFD for 6 months to induce liver fibrosis. Oxidized low density lipoprotein (oxLDL) were used to induce the activation of hepatic stellate cells and fibrosis in mouse HSCs and human LX-2 cells. H&E, Masson’s trichrome staining and Sirius red staining were used for liver sections. Protein and mRNA expressions were evaluated with Western blot and RT-PCR, respectively. Results: FNDC5 deficiency aggravated the HFD-induced liver fibrosis and HSCs activation in mice. It exacerbated the HFD-induced inhibition of AMPK phosphorylation, upregulation of connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β), and deposition of extracellular matrix (ECM) in liver of mice. Administration of FNDC5 attenuated oxLDL-induced AMPK deactivation, HSCs activation, CTGF and TGF-β upregulation and ECM deposition in mouse HSCs. The beneficial effects of FNDC5 on oxLDL-induced AMPK dephosphorylation, HSCs activation and ECM deposition were prevented by the inhibition of AMPK with compound C in human LX-2 cells. However, the effects of FNDC5 on hepatic fibrosis in vivo in this study cannot be distinguished from its effects on adiposity and hepatic steatosis. Conclusions: FNDC5 deficiency aggravates HFD-induced liver fibrosis in mice. FNDC5 plays beneficial roles in attenuating liver fibrosis via AMPK phosphorylation-mediated inhibition of HSCs activation.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yani Wang ◽  
Huibin Liu ◽  
Na Sun ◽  
Jing Li ◽  
Xiang Peng ◽  
...  

Ischemia-reperfusion injury (IRI) is defined as the total combined damage that occurs during a period of ischemia and following the recovery of blood flow. Oxidative stress, mitochondrial dysfunction, and an inflammatory response are factors contributing to IRI-related damage that can each result in cell death. Irisin is a polypeptide that is proteolytically cleaved from the extracellular domain of fibronectin type III domain-containing protein 5 (FNDC5). Irisin acts as a myokine that potentially mediates beneficial effects of exercise by reducing oxidative stress, improving mitochondrial fitness, and suppressing inflammation. The existing literature also suggests a possible link between irisin and IRI, involving mechanisms similar to those associated with exercise. This article will review the pathogenesis of IRI and the potential benefits and current limitations of irisin as a therapeutic strategy for IRI, while highlighting the mechanistic correlations between irisin and IRI.


2021 ◽  
Vol 11 (15) ◽  
pp. 7120
Author(s):  
Mirko Pesce ◽  
Irene La Fratta ◽  
Teresa Paolucci ◽  
Alfredo Grilli ◽  
Antonia Patruno ◽  
...  

The beneficial effects of exercise on the brain are well known. In general, exercise offers an effective way to improve cognitive function in all ages, particularly in the elderly, who are considered the most vulnerable to neurodegenerative disorders. In this regard, myokines, hormones secreted by muscle in response to exercise, have recently gained attention as beneficial mediators. Irisin is a novel exercise-induced myokine, that modulates several bodily processes, such as glucose homeostasis, and reduces systemic inflammation. Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The FNDC5/irisin system is also expressed in the hippocampus, where it stimulates the expression of the neurotrophin brain-derived neurotrophic factor in this area that is associated with learning and memory. In this review, we aimed to discuss the role of irisin as a key mediator of the beneficial effects of exercise on synaptic plasticity and memory in the elderly, suggesting its roles within the main promoters of the beneficial effects of exercise on the brain.


Biomaterials ◽  
2013 ◽  
Vol 34 (16) ◽  
pp. 4191-4201 ◽  
Author(s):  
Hayato Matsui ◽  
Fuminori Sakurai ◽  
Kazufumi Katayama ◽  
Yasuhiro Abe ◽  
Mitsuhiro Machitani ◽  
...  

2011 ◽  
Vol 100 (3) ◽  
pp. 604a
Author(s):  
Andras Czajlik ◽  
Gary Thompson ◽  
Ghulam N. Khan ◽  
Arnout Kalverde ◽  
Steve W. Homans ◽  
...  

2018 ◽  
Vol 50 (4) ◽  
pp. 1574-1584 ◽  
Author(s):  
Xiu-ying Yang ◽  
Margaret C.L. Tse ◽  
Xiang Hu ◽  
Wei-hua Jia ◽  
Guan-hua Du ◽  
...  

Background/Aims: Fibronectin type III domain-containing protein 5 (FNDC5), also known as irisin, is a myokine secreted from muscle in response to exercise. However, the molecular mechanisms that regulate FNDC5 expression and the functional significance of irisn in skeletal muscle remain unknown. In this study, we explored the potential pathways that induce FNDC5 expression and delineated the metabolic effects of irisin on skeletal muscle. Methods: C2C12 myotubes were treated with drugs at various concentrations and durations. The expression and activation of genes were measured by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Oxidative phosphorylation was quantified by measuring the oxygen consumption rate (OCR). Results: We found that the exercise-mimicking treatment (cAMP, forskolin and isoproterenol) increased Fndc5 expression in C2C12 myotubes. CREB over-expressed C2C12 myotubes displayed higher Fndc5 expression. CREB over-expression also promoted peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) expression. PGC-1α-induced Fndc5 expression was blocked when the dominant negative form of CREB (S133A) was present. PGC-1α mutation (S570A) also decreased Fndc5 expression. Immunoprecipitation showed that overexpressed PGC-1α complexed with CREB in HEK293 cells. C2C12 myotubes treated with forskolin also increased endogenous CREB and PGC-1α binding. Functionally, irisin treatment increased mitochondrial respiration, enhanced ATP production, promoted fatty acid oxidation but decreased glycolysis in myotubes. Conclusion: Our observation indicates that cAMP-mediated PGC-1α/CREB interaction triggers Fndc5 expression, which acts as an autocrine/paracrine to shape the metabolic phenotype of myotubes.


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