SummaryBackground/PurposeIrisin is a skeletal muscle myokine that causes the brown coloration of white fat, promotes fat burning, inhibits weight gain and may be useful for treatment of obesity. Irisin is also related to glucose/lipid metabolism and may prevent onset of diabetes, but a consensus on irisin secretion has not been reached. The purpose of this study was to determine the relationships between serum irisin levels and physical factors in untreated Japanese men and women with obesity.MethodsThe subjects were 66 untreated patients with obesity (body mass index ≥30 kg m−2) who visited our obesity clinic. The subjects included 19 men and 47 women with a mean age of 45.7 ± 13.4 years, mean body weight of 93.8 ± 17.6 kg, and mean body mass index of 36.5 ± 4.7 kg m−2. At the initial visit, blood sampling was performed, body composition was evaluated using dual energy X‐ray absorptiometry, and exercise tolerance was determined in a cardiopulmonary exercise test. Homeostasis model of assessment – insulin resistance (HOMA‐IR), an index of insulin resistance, and the serum level of irisin were measured.ResultsIn men, serum irisin was positively correlated with fasting blood glucose (r = 0.491, P < 0.05), immunoreactive insulin (r = 0.536, P < 0.05), HOMA‐IR (r = 0.635, P < 0.01), body weight (r = 0.491, P < 0.05), lean body mass of the trunk (r = 0.579, P < 0.05) and whole lean body mass (r = 0.489, P < 0.05). In women, serum irisin was positively correlated with immunoreactive insulin (r = 0.502, P < 0.01) and HOMA‐IR (r = 0.385, P < 0.01). In both sexes, HOMA‐IR was an independent variable associated with obesity (men: β = 0.635, R2 = 0.369, P < 0.01; women: β = 0.385, R2 = 0.129, P < 0.01).ConclusionThe serum level of irisin was positively correlated with HOMA‐IR in Japanese patients with obesity of both sexes. This suggests that compensatory enhancement of irisin secretion may occur in response to insulin resistance.