FNDC5/Irisin: Physiology and Pathophysiology

Abstract

A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

Circulating Irisin in Children and Adolescents With Prader-Willi Syndrome: Relation With Glucose Metabolism

“…Irisin, a myokine that induces the browning of WAT and regulates the transcription of thermogenic genes ( 16 ), has recently attracted attention for its potential role in obesity and metabolic syndrome via regulation of WAT accumulation and body weight control ( 48 ).…”

“…In children, the direction of the relationship between irisin levels and obesity is debated ( 25 ), with some authors reporting unaltered or even decreased irisin levels ( 28 , 48 ), and others showing higher irisin levels in obese children as compared with healthy controls ( 28 , 35 , 49 ). Potential reasons for such discrepancy involve the role of peripubertal development on the interplay between fat mass, muscle, and fat/muscle mass ratio ( 25 ), as well as the potential for irisin to be secreted as a myokine in condition of healthy body weight ( 16 , 50 , 51 ) and as an adipokine in condition of fat accumulation ( 17 , 20 , 23 ).…”

Expression of Irisin/FNDC5 in Breast Cancer

“…The deglycosylated form of irisin ranges from 12 to 15k Da. N-glycosylation has a crucial role in the biological activity of irisin [ 5 ]. Irisin was first detected in mouse skeletal muscle fibers in 2012 by Boström et al [ 6 ].…”

Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches

“…Irisin is a newly identified hormone known to have a protective effect against synapse failure and cognitive decline in AD-related pathologies [ 13 ]. It has been reported that irisin is secreted in the heart, liver, pancreas, and testes, and it crosses the blood–brain barrier [ 13 , 14 ].In the brain, irisin regulates brain-derived neurotrophic factor (BDNF) expression and helps in protecting the neuronal damage caused by oxidative stress [ 15 , 16 ].…”

“…Moreover, it has also been demonstrated that FNDC5/irisin interacts with the amyloid precursor protein (APP) and regulates Aβ level in the brain [ 14 , 17 ]. Therefore, it is speculated that using irisin as a drug carrier for the drugs approved for AD-related pathology could be a promising strategy for treating AD.…”