Endocrine Abstracts

Irisin is a myokine involved in the browning of white adipose tissue and in the regulation of energy expenditure, glucose tolerance and insulin sensitivity. It was previously demonstrated that obese adults with Prader-Willi syndrome (PWS) harbor lower irisin levels than individuals with common obesity. Significant associations seem to relate irisin to muscle mass, REE, insulin resistance and triglycerides and also the strongest independent predictors of irisin levels were PWS status, %FM and triglycerides (Mai S et al., 2020). The divergent models of obesity herein studied suggest a potential link between circulating irisin and muscle mass and metabolic dysfunction relating to adiposity. Scanty and debated information exists on the role played by irisin in obese children. In this context, the obese phenotype of children with PWS markedly differs from that of BMI-matched subjects with common obesity. Based on these considerations, the present study aimed at exploring circulating irisin in relation to body composition and metabolic profile in obese children with and without PWS. For this purpose, 25 PWS children and adolescents (15 DEL15/10 UPD15, 16 M/9 F; age 6.6-17.8y; BMI SDs 2.5±0.3) and 25 age, and BMI-matched control subjects (11 M/14 F; age 6.8-18.0y; BMI SDs, 2.8±0.1) underwent analysis of irisin levels, body composition and metabolic profile, in particular glucose homeostasis assessed by OGTT. Expected differences in body composition and metabolic profile existed between study groups. PWS displayed lower FFM (P<0.05), as well as lower fasting insulin level (P<0.0001), 2h post-OGTT insulin (P<0.05) and C-peptide levels (P<0.0001), together with better insulin resistance, expressed as HOMA-IR (P<0.0001). Irisin levels were significantly lower in PWS group than in controls with common obesity (P<0.05): more specifically, irisin levels of PWS patients with DEL15 were reduced compared to controls with common obesity (P<0.05). Exploring the relation between irisin and glucose metabolism in obesity, univariate correlation analysis in our obese population as a whole showed positive associations between irisin, insulin OGTT₀ (P<0.05), insulin OGTT₁₂₀ (P<0.005), HOMA-IR (P<0.05) and C-peptide (P<0.05). In stepwise multivariable regression analysis on merged data, irisin levels were independently predicted by insulin OGTT₁₂₀. Overall, current results show that irisin levels are lower in obese PWS compared to matched children, possibly due to differences in body composition and insulin resistance. A strong association links irisin to measures of insulin resistance, particularly post-OGTT insulin levels, suggesting a link between this myokine and insulin sensitivity in our two divergent models of obesity.