# Role of Irisin in Endocrine and Metabolic Disorders--Possible New Therapeutic Agent?
## 2 General Data  
Irisin is an approximately 12 kDa hormone-like polypeptide which is produced by proteolytic cleavage of its precursor, FNDC5. The crystal structure of irisin comprises an N-terminal fibronectin 3 (FNIII)-like domain (residues 30-123) and a flexible C-terminal tail (residues 124-140) [13]. Irisine is a myokine, which is secreted following physical activity. Even though skeletal muscle is the source of 72% of the total amount of circulating irisin, several studies have also suggested other sources, such as pancreatic islets or white adipocyte cells [14]. Recent studies have indicated that irisin acts mostly through mitogen-activated protein kinase (MAPK) signaling pathways, which are involved in neural differentiation, browning of white adipocytes, and osteoblast proliferation, among others. Other essential functions of irisin are mediated through additional pathways, including the 5\({}^{\prime}\) 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 [15]. Irisin may exert its effects through \(\alpha\)V integrin receptors [14].  
Apart from the muscle and adipose tissue, irisin is also well-distributed in other organs and tissues, including the cerebrospinal fluid, cerebellum, thyroid, pineal gland, liver, pancreas, testis, spleen, and stomach of adults and fetuses [1].  
Regarding the actions of irisin, numerous studies in animal (mice and rat) models and humans have been carried out, with similar or contradictory results.  
The main actions of irisin, at the level of the brain, bone, muscle, adipose tissue, liver, pancreas, and heart, are presented in Figure 1.  
Irisin acts at the central nervous system level by increasing the multiplication of hippocampal neurons [16] and the expression of brain-derived neurotrophic factor (BDNF); it also plays an important role in neurogenesis and controls feeding behavior through the regulation of peptides/neurotransmitters [1; 17; 18].  
In the skeletal muscle, irisin induces mitochondrial biogenesis [19], stimulates myogenesis by amplifying positive regulators in skeletal muscles [20], and acts as a protection factor against bone loss and muscle atrophy [1].  
Cardiovascular and endothelial functions are influenced by irisin, in terms of vasorelasation and decreased oxidative stress [1; 21; 22].  
The most important and promising actions of irisin involve glucose and lipid homeostasis. The reduction in hepatic insulin resistance, weight and blood glucose levels, inhibition of gluconeogenesis, and stimulation of glycogenesis are the main metabolic effects attributable to irisin [1; 23; 24].  
There is some debate regarding the measurement of irisin, with uncertain \"normal\" values of irisin in humans as a consequence. The currently available irisin antibodies still bind to unspecific serum proteins, thus limiting irisin measurement by ELISA. The measurement of irisin with labeled peptides by mass spectrometry is a more accurate method, but requires a complex methodology [25]. Finding a reliable method for irisin determination is mandatory for future studies of this protein, both in humans and experimental animals.