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

Abstract

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.

Cardiorespiratory Fitness and Muscular Strength Moderates the Relationship between FNDC5 Polymorphism and Adiposity in Children and Adolescents

“…Irisin is, therefore, associated with muscle mass, strength, and metabolism. However, the role of the expressed form of irisin, concerning physiological functions and circulating levels, remains controversial in humans [ 20 ]. Thus, the genetic evaluation of FNDC5 can be useful to identify patterns of metabolic health and disease [ 21 ] with promising expectation in the treatment of obesity [ 20 ].…”

Irisin stimulates the release of CXCL1 from differentiating human subcutaneous and deep-neck derived adipocytes via upregulation of NFκB pathway

“…Furthermore, it is present in the cerebrospinal fluid, liver, pancreas, stomach, saliva, and urine (40). Controversial effects were observed when differentiating human adipocytes of distinct anatomical origins were treated with the recombinant hormone ( 21), ( 22), ( 23), ( 24), ( 25), ( 26), (41). We reported that irisin induced a beige phenotype of human primary abdominal subcutaneous and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes when they were treated at a concentration detected in physically active rodents on top the white adipogenic protocol that was used in this study (26), (25).…”

Moderate-intensity exercise might be a competitive protocol to prevent obesity and obesity-related metabolic diseases

“…Physical activity can promote health and lower the incidence of multifarious diseases over numerous molecular pathways and cytokines such as myokines, adipokines, and hepatokines [39]. Irisin can increase browning of WAT [6][7][8], increase glucose uptake [11], improve fatty acid oxidation [12], increase lipolysis [40], improve insulin resistance [14,15], decrease body weight [7,13], and improve metabolism [9,40].…”