Exercise response: Is irisin a novel factor that explains the metabolic adaptation?

Abstract

Exercise is a cornerstone in the management of metabolic conditions like obesity and type 2 diabetes (T2D), yet substantial variation exists in individual responses. Irisin, an exercise-induced myokine involved in regulating adipose tissue and glucose metabolism, may contribute to this heterogeneity. However, its precise quantification and exercise-induced responses remain unclear due to analytical discrepancies and inconsistent findings across study designs and populations. To address these gaps, this dissertation comprehensively examined exercise-induced irisin responses across metabolic health statuses and exercise intensities. The objectives were to: evaluate the analytical performance of irisin ELISA kits; assess acute irisin responses across different exercise intensities in individuals of varying obesity and insulin sensitivity status; and investigate the impact of increasing intensity on chronic exercise adaptations, along with irisin’s predictive role in glycemic improvements. This dissertation consisted of three projects. First, the agreement, between-day reliability, and within-subject precision of two commercially available irisin ELISA kits was evaluated. Second, acute irisin responses were assessed in a randomized controlled crossover trial, where adults with overweight/obesity (OW/OB) or a healthy weight completed acute bouts of moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), and rest. Third, a secondary analysis of the INTENSITY trial examined the impact of increasing exercise intensity on irisin and its association with individual glycemic responses in individuals with prediabetes/T2D who completed a 28- week aerobic training (AT) intervention. Significant bias was identified between ELISA kits, with R&D Systems demonstrating superior reliability and precision compared to Phoenix Pharmaceuticals. OW/OB exhibited lower circulating irisin that only increased after acute HIIT but not MICT. Irisin was positively correlated with insulin sensitivity in healthy weight and not OW/OB. Circulating irisin remained unchanged across the AT intervention at the group-level; minor, individual increases in irisin predicted glycemic improvements. This dissertation offers novel insights into irisin’s role in exercise metabolism, revealing distinct acute and chronic adaptations with robust quantification. Higher exercise intensities may be necessary for acute irisin responses in OW/OB. In individuals with prediabetes/T2D, no chronic adaptations were observed regardless of intensity; yet, minor individual increases predicted glycemic improvements. These findings support the development of targeted strategies for personalized exercise prescription.