Irisin: A renaissance in metabolism?

Some studies report decreased circulating irisin in obese populations following training, potentially related to improvement of irisin resistance, a compensatory elevation in obesity due to reduced target tissue sensitivity.

“some studies report decreased circulating irisin in obese populations following training, potentially related to improvement of irisin resistance—a compensatory elevation in obesity due to reduced target tissue sensitivity [19,42,43].”

Myokine resistance-observed for irisin and FGF21 in obese and diabetic states-complicates interpretation, as elevated circulating levels may reflect target tissue insensitivity rather than enhanced function.

“Third, the phenomenon of myokine resistance—observed for irisin [42,43] and FGF21 [51,52] in obese and diabetic states—complicates interpretation, as elevated circulating levels may reflect target tissue insensitivity rather than enhanced function.”

Medication use, circadian and nutritional state, and assay variability are confounders that most primary studies do not account for.

“Other less frequently discussed confounders include medication use (statins, metformin, GLP-1 agonists could influence circulating myokine levels independently of exercise, but most primary studies do not account for this), circadian and nutritional state (many myokines exhibit diurnal rhythms and may be sensitive to fasting/feeding status), and assay variability (irisin measurements, for example,”

Training status can affect both baseline and exercise-induced myokine levels; individuals with metabolic syndrome exhibit attenuated irisin responses, and failure to distinguish acute and chronic measurement time points may have contributed to contradictory findings.

“Training status can affect both baseline and exercise-induced myokine levels. For instance, individuals with metabolic syndrome have been found to exhibit attenuated irisin responses [19], and failure to distinguish between acute and chronic measurement time points may have contributed to some contradictory findings in the literature [18,42,50,80].”