Serum adipokines in Duchenne muscular dystrophy: relationships to BMI, corticosteroids, and muscle fat fraction

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder hallmarked by muscle degeneration, replacement by fat, and weakness. Corticosteroids slow disease progression, but they also cause metabolic disruptions such as significant weight gain. For this preliminary study, we evaluated levels of serum adipokines, or factors released by adipose tissue, in a large cohort of individuals with DMD. 309 serum samples were collected from 94 participants with DMD (longitudinal samples) and 14 controls (one time point) enrolled in the ImagingDMD natural history study. Large-scale serum proteomics were conducted using the SomaScan platform. Targeted analysis was performed on 11 adipokines including leptin, adiponectin, resistin, visfatin, chemerin, omentin, ghrelin, obestatin, apelin, retinol binding protein (RBP), and vaspin. Levels were evaluated in relation to diagnosis, corticosteroid use, body mass index (BMI), and soleus muscle fat fraction, which was determined by magnetic resonance spectroscopy. Correcting for multiple comparisons, leptin, resistin, ghrelin, omentin, apelin, RBP, and vaspin levels were different in control and DMD serum, while RBP differed between serum from corticosteroid treated (n=268) and untreated individuals with DMD (n=14). BMI was strongly correlated with leptin (r=0.79) and weakly correlated with resistin, omentin, ghrelin, apelin, and RBP. When taking BMI into account, soleus muscle fat fraction was independently correlated with leptin (p<0.0001), adiponectin (p<0.0001), omentin (p=0.0003), and ghrelin levels (p=0.0011). Overall, 8 of 11 adipokines were altered in DMD, and 7 were correlated with BMI. Correlations between muscle fat fraction and leptin, adiponectin, omentin, and ghrelin levels were independent from BMI, suggesting they may be released from muscle fat. These preliminary results will be expanded to assess adipokine levels in an independent cohort from the Netherlands with different patterns of corticosteroid use. Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder hallmarked by muscle degeneration, replacement by fat, and weakness. Corticosteroids slow disease progression, but they also cause metabolic disruptions such as significant weight gain. For this preliminary study, we evaluated levels of serum adipokines, or factors released by adipose tissue, in a large cohort of individuals with DMD. 309 serum samples were collected from 94 participants with DMD (longitudinal samples) and 14 controls (one time point) enrolled in the ImagingDMD natural history study. Large-scale serum proteomics were conducted using the SomaScan platform. Targeted analysis was performed on 11 adipokines including leptin, adiponectin, resistin, visfatin, chemerin, omentin, ghrelin, obestatin, apelin, retinol binding protein (RBP), and vaspin. Levels were evaluated in relation to diagnosis, corticosteroid use, body mass index (BMI), and soleus muscle fat fraction, which was determined by magnetic resonance spectroscopy. Correcting for multiple comparisons, leptin, resistin, ghrelin, omentin, apelin, RBP, and vaspin levels were different in control and DMD serum, while RBP differed between serum from corticosteroid treated (n=268) and untreated individuals with DMD (n=14). BMI was strongly correlated with leptin (r=0.79) and weakly correlated with resistin, omentin, ghrelin, apelin, and RBP. When taking BMI into account, soleus muscle fat fraction was independently correlated with leptin (p<0.0001), adiponectin (p<0.0001), omentin (p=0.0003), and ghrelin levels (p=0.0011). Overall, 8 of 11 adipokines were altered in DMD, and 7 were correlated with BMI. Correlations between muscle fat fraction and leptin, adiponectin, omentin, and ghrelin levels were independent from BMI, suggesting they may be released from muscle fat. These preliminary results will be expanded to assess adipokine levels in an independent cohort from the Netherlands with different patterns of corticosteroid use.