New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

Rabiee, Farzaneh; Lachinani, Liana; Ghaedi, Sarvenaz; Nasr-Esfahani, Mohammad Hossein; Megraw, Timothy L.; Ghaedi, Kamran

doi:10.1186/s13578-020-00413-3

Cited by 108 publications

(91 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, we found that the browning effect induced by irisin was mediated by p38 MAP kinase and ERK MAP kinase signaling [ 79 ]. In addition, irisin has also been shown to exert its browning and other essential functions through additional pathways [ 80 , 81 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity

Wang

Yang

et al. 2021

International Journal of Endocrinology

View full text Add to dashboard Cite

Obesity is a worldwide health problem due to the imbalance of energy intake and energy expenditure. Irisin, a newly identified exercise-responsive myokine, which is produced by the proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a promising therapeutic strategy to combat obesity and obesity-related complications. Various studies in mice have shown that irisin could respond to systematic exercise training and promote white-to-brown fat transdifferentiation, but the role and function of irisin in humans are controversial. In this review, we systematically introduced and analyzed the factors that may contribute to these inconsistent results. Furthermore, we also described the potential anti-inflammatory properties of irisin under a variety of inflammatory conditions. Finally, the review discussed the existing unresolved issues and controversies about irisin, including the transcription of the irisin precursor FNDC5 gene in humans, the cleavage site of the yet unknown proteolytic enzyme that cleaves irisin from FNDC5, and the reliability of irisin levels measured with available detection methods.

show abstract

Section: Introductionmentioning

confidence: 99%

The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity

Wang

Yang

et al. 2021

International Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Skeletal muscle is the main source of irisin production. Irisin has numerous physiological functions including thermogenesis, glucose metabolism, increased metabolism, differentiation, and proliferation [5].…”

Section: Introductionmentioning

confidence: 99%

“…Exercise caused the expression of PGC-1α in skeletal muscle, encouraging the cleavage of FNDC5 to irisin. Irisin is firstly identified as a PGC-1α supported myokine with the ability to induce murine brown-fatlike development of white adipose tissue [5].…”

Section: Introductionmentioning

confidence: 99%

Role of swimming on muscle PGC-1α, FNDC5 mRNA, and assessment of serum omentin, adropin, and irisin in high carbohydrate high fat (HCHF) diet induced obesity in rats

Badawy

El-Laithy

Morsy

et al. 2020

Egypt J Med Hum Genet

View full text Add to dashboard Cite

Background Exercise benefits a variety of organ systems in mammals, and some of the best recognized effects of exercise on muscle are mediated by the transcriptional peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC-1α). The regulatory effect of swimming on muscle PGC-1α, FNDC5 mRNA expression, and subsequently irisin levels is more controversial. This study aimed to investigate the role of swimming as an exercise on the expression of peroxisome proliferator-activated receptor-gamma coactivator1 alpha (PGC-1α) and Fibronectin type III domain containing 5 (FNDC5) mRNA in skeletal muscle and assessment of serum omentin, adropin, irisin, and PGC-1α levels in high carbohydrate high fat (HCHF) diet induced obesity in rats. Sixty male albino rats are randomly divided into 4 groups (15 rats/group). In the first group (control), rats are fed with standard diet. The 2nd group (cont + swim) is fed on standard diet and made swimming exercise. The 3rd group of rats is fed on HCHF, whereas in the 4th group (HCHF + swim) is also fed on HCHF diet and made swimming exercise for 20 weeks. Blood glucose, insulin, HOMA-IR, lipid profile, omentin, irisin, adropin, and PGC-1α were measured. Also, FNDC5 and PGC-1α are extracted and purified from muscle tissue samples measured by PCR test. Results Our results showed significant increase in glucose, insulin, insulin resistance, cholesterol, and triglycerides with significant decrease in omentin, irisin, adropin, PGC-1α, and HDL in HCHF group as compared to the control group. These results improved after exercise in all parameter in HCHF + swim group compare to HCHF group. Also, there was inverse correlation between omentin and fasting glucose and HOMA-IR in HCHF + swim group. Conclusions It concluded that swimming exercise improved all the above measured parameters in serum and tissues which might have been promising for the prevention of metabolic diseases.

show abstract

“…The identification of the irisin receptor is still a challenge; however, the intracellular signaling pathways activated by irisin have been partially elucidated. Irisin principally exerts its biological functions via mitogen-activated protein kinases (MAPK) signaling; nonetheless, 5′ adenosine monophosphate-activated protein kinase (AMPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and signal transducer and activator of transcription 3 (STAT3)/Snail pathways are also involved in additional effects [ 28 ]. In the brain, recent studies demonstrated that the irisin neuroprotective role seems to be mediated by both STAT3 and cyclic adenosine 3′,5′-monophosphate/protein kinase A/cAMP response element-binding protein (cAMP/PKA/CREB) signaling pathways [ 29 , 30 ].…”

Section: Overview Of Fndc5/irisin Systemmentioning

confidence: 99%

FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

Pignataro

Dicarlo

Zerlotin

et al. 2021

IJMS

View full text Add to dashboard Cite

Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC1α control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND.

show abstract

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

Cited by 108 publications

References 89 publications

The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity

The Effect of Irisin as a Metabolic Regulator and Its Therapeutic Potential for Obesity

Role of swimming on muscle PGC-1α, FNDC5 mRNA, and assessment of serum omentin, adropin, and irisin in high carbohydrate high fat (HCHF) diet induced obesity in rats

FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

Contact Info

Product

Resources

About