Irisin has been proposed to be a myokine mediating the effect of exercise on adipocyte browning. The physiology of irisin in humans is not completely understood. To study the physiology of irisin in healthy individuals with different age and fitness levels and to explore the direct effects of irisin on muscle metabolism. Treadmill exercise studies were conducted to measure circulating irisin at baseline and in response to exercise among old and young, physically active and sedentary individuals. Also, high- and moderate-intensity swimming was performed in adolescent men and women to study the effect of exercise intensity and the time course of irisin induction by acute bouts of exercise. Human myotubes were treated with recombinant irisin, and the effect on gene expression, cell signaling, and metabolism was examined. Baseline circulating irisin was lower in old (vs young) and physically active (vs sedentary) subjects. Despite differences in basal levels, the percentage increase of irisin by acute bouts of exercise was not related to age or fitness level. The time course study revealed that circulating irisin increased immediately after high-intensity interval exercise and declined 1 hour thereafter. In vitro experiments showed that irisin facilitates glucose and lipid metabolism in human muscle through AMP kinase phosphorylation. Despite the differences in basal irisin levels, exercise-induced irisin secretion is independent of age or fitness level. Increased irisin can directly modulate muscle metabolism through AMP kinase activation.

The myokine irisin may increase energy expenditure and affect metabolism. The objective of the study was to elucidate predictors of irisin and study whether circulating irisin may have day-night rhythm in humans. This was an observational, cross-sectional study with an additional 24-hour prospective observational arm (day-night rhythm substudy) and two prospective interventional arms (mixed meal substudy and exercise substudy). The study was conducted at the Hellenic Military School of Medicine (Thessaloniki, Greece). One hundred twenty-two healthy, young individuals were subjected to anthropometric and body composition measurements, and their eating and exercise behavior profiles were assessed with validated questionnaires. Subgroups were subjected to day-night rhythm, standardized meal ingestion, and 30-minute aerobic exercise studies. Circulating irisin levels were measured. Ιrisin levels were lower in males than females (P = .02) after adjustment for lean body mass, which was its major determinant. Irisin levels followed a day-night rhythm (P < .001) with peak at 9:00 pm. Irisin levels were increased at the end of exercise (84.1 ± 10.0 vs 105.8 ± 14.3 ng/mL; P < .001). Irisin levels were not affected by intake of a standardized meal and were not associated with caloric intake or diet quality. In healthy, young individuals, circulating irisin displays a day-night rhythm, is correlated with lean body mass, and increases acutely after exercise.

Objective: Exercise improves weight status and metabolism. Irisin, a novel myokine, may be involved in the regulation of metabolic function. The effect of an exercise and dietary lifestyle intervention for 1‐year on irisin, adipokines (leptin, adiponectin, resistin) and inflammatory markers (C‐reactive protein (CRP), soluble tumor necrosis factor receptor II (sTNFR‐II) was evaluated, and predictors of irisin levels were characterized in obese children.Methods: Parameters were assessed at baseline and at follow‐up for 65 obese children who completed the program (7–18 years, 54%boys). Their relation to weight status and metabolic risk was analyzed.Results: Anthropometric and metabolic parameters improved after completion of the program. Circulating irisin levels at baseline were 111.0 ± 8.0 ng ml⁻¹ and increased after the intervention by 12% [6%, 17%], P = 0.00003. There was no evidence for differences in irisin levels between genders and across age. Moreover, changes in irisin did not correlate with those in BMI‐SDS, adipokines or inflammatory markers. Leptin decreased after the intervention (Δ5.3 ng ml⁻¹, [3.2, 6.3], P = 10⁻⁷). Anthropometric measures were significantly associated with leptin and inflammatory markers.Conclusions: A 1‐year long lifestyle intervention program is associated with improvement in anthropometric and metabolic parameters and leads to an elevation in irisin levels in obese children.