text: Irisin (fibronectin type III domain-containing protein 5 or FNDC5), a recently described myokine hormone produced and secreted by acutely exercising skeletal muscles, is thought to bind white adipose tissue cells via undetermined receptors. Irisin has been reported to promote a brown adipose tissue-like phenotype upon white adipose tissue by increasing cellular mitochondrial density and expression of uncoupling protein-1, thereby increasing adipose tissue energy expenditure via thermogenesis. This is considered important, because excess visceral adipose tissue in particular distorts the whole body energy homeostasis, increases the risk of cardiovascular disease and raises exposure to a milieu of adipose tissue-secreted hormones (adipokines) that promote inflammation and cellular aging. The authors enquired whether the favorable impact of irisin on white adipose tissue might be associated with maintenance of telomere length, a well-established genetic marker in the aging process.  They conclude that these data support the view that irisin may have a role in the modulation not only of energy balance but also the aging process.
  However, exogenous irisin may aid in heightening energy expenditure, and thus in reducing obesity. Boström et al. reported on December 14, 2012: "Since the conservation of calories would likely provide an overall survival advantage for mammals, it appears paradoxical that exercise would stimulate the secretion of a polypeptide hormone that increases thermogenesis and energy expenditure. One explanation for the increased irisin expression with exercise in mouse and man may have evolved as a consequence of muscle contraction during shivering. Muscle secretion of a hormone that activates adipose thermogenesis during this process might provide a broader, more robust defense against hypothermia. The therapeutic potential of irisin is obvious. Exogenously administered irisin induces the browning of subcutaneous fat and thermogenesis, and it presumably could be prepared and delivered as an injectable polypeptide. Increased formation of brown or beige/brite fat has been shown to have anti-obesity, anti-diabetic effects in multiple murine models, and adult humans have significant deposits of UCP1-positive brown fat. (Our data show) that even relatively short treatments of obese mice with irisin improves glucose homeostasis and causes a small weight loss. Whether longer treatments with irisin and/or higher doses would cause more weight loss remains to be determined. The worldwide, explosive increase in obesity and diabetes strongly suggests exploring the clinical utility of irisin in these and related disorders. Another potentially important aspect of this work relates to other beneficial effects of exercise, especially in some diseases for which no effective treatments exist. The clinical data linking exercise with health benefits in many other diseases suggests that irisin could also have significant effects in these disorders."
  While the murine findings reported by Boström et al. appear encouraging, other researchers have questioned whether irisin operates in a similar manner in humans. For example, Timmons et al. noted that over 1,000 genes are upregulated by exercise and examined how expression of FNDC5 was affected by exercise in ~200 humans. They found that it was upregulated only in highly active elderly humans, casting doubt on the conclusions of Boström et al. Further discussion of this issue can be found in .