Individuals with PWS require marked caloric restriction and daily exercise to prevent morbid obesity. Lower energy expenditure, hypotonia, decreased muscle mass, and cognitive impairment make exercise challenging for this population. Exercise guidelines include resistance training as an important component. Myokine responses to resistance exercise may mediate beneficial metabolic effects. We aimed to determine if young PWS adults can perform a resistance exercise program and to measure myokine responses in PWS versus age-and BMI-matched controls. Each group included 11 participants (7M/4F). Ages and BMI for PWS and controls were 30.7 ± 4.6 versus 30.1 ± 4.3 years and 28.3 ± 4.3 versus 28.2 ± 4.2 kg/m 2 , respectively.Glucose, creatine kinase (CK), lactate, and myokines were measured before, after, 30, and 60 min after completing eight resistance exercises. Myokines were assayed using a multiplex myokine panel (Merck Millipore). CK was lower in PWS versus controls (62 ± 16 vs.322 ± 100 U/L, p < .04). Peak lactate was 3.7 ± 0.7 in PWS versus 7.3 ± 0.7 mmol/Lin controls (p < .001). The increase in interleukin-6 was similar in PWS and controls (41 ± 16% and 35 ± 10%, respectively). Pre-and post-exercise levels of the six myokines assayed showed no consistent differences between the PWS and control participants. PWS young adults are capable of performing resistance/strength-building exercise. The lower CK and peak lactate levels in PWS may reflect decreased muscle mass in this population. Further studies are needed to determine optimal exercise regimens and assess the role of myokines incontributing to the metabolic phenotype of PWS. K E Y W O R D Sbrain-derived neurotropic factor (BDNF), exercise, interleukin-6 (IL-6), lactate, obesity

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Background: Individuals with PWS require marked caloric restriction and daily exercise to prevent morbid obesity. Lower energy expenditure compared to BMI-matched controls along with hypotonia, decreased muscle mass, and cognitive impairment make exercise particularly challenging for this population. Exercise guidelines include resistance training as an important component. Myokine responses to resistance exercise may have beneficial metabolic effects. Objectives: Determine if young PWS adults can perform a resistance exercise program. Evaluate myokine responses to acute resistance exercise in young adults with PWS and compare responses with age and BMI-matched controls. Methods: Each study group included 11 participants (7M/4F). Mean±SD ages were 30.7±4.6 and 30.1±4.3 years for PWS and controls (NS). BMI values were 28.3±4.3 and 28.2±4.2 kg/m 2 for PWS and controls, respectively (NS). Blood samples for glucose, creatine kinase (CK), lactate, hemoglobin A1c (HbA1C) and myokines were obtained before performing a program of eight resistance exercises lasting 45-60 minutes. Additional blood samples were drawn immediately after, and 30 and 60 minutes after completing the exercises. Myokines were assayed using a multiplex myokine panel (Merck Millipore). Paired t-test was used for comparing results for PWS vs controls. The unpaired t-test was used for comparing peak laboratory values with basal levels. Results: Basal levels (mean±SEM) of glucose, hemoglobin A1c, and lactate were similar for PWS and controls but CK was lower in PWS vs controls (62±16 vs 322±100 U/L, p<0.04). Peak lactate was 3.7±0.7 in PWS vs 7.3±0.7 mmol/l in controls (p<0.001). Basal and peak levels of interleukin-6 (IL-6), brain-derived neurotropic factor (BDNF), irisin, osteonectin, myostatin, and fibroblast growth factor-21 varied widely and no statistically significant differences were found between the two groups. Post-exercise IL-6 increased by 41±16 % in PWS (p<0.03) and 35±10 % in controls (p<0.007). Post-exercise BDNF rose to 47±18% over baseline in control males (p<0.006) but not in PWS males, or in PWS and control females. Failure to increase BDNF and irisin levels following exercise was associated with significantly lower strength as determined by maximum weights used. Conclusions: PWS young adults are capable of performing resistance/strength-building exercise. The lower CK and peak lactate levels in PWS reflect decreased muscle mass in this population. IL-6 increased significantly in both PWS and control groups. Increases in BDNF and irisin were associated with greater exertion compared to non-responders. Resistance exercise should be part of the daily sports regimen for individuals with PWS. Further studies of myokine levels in PWS are needed to characterize the unique metabolic phenotype in this population and assist in prescribing appropriate personalized exercise programs.