Obesity Is Associated With Gene Expression and Imaging Markers of Iron Accumulation in Skeletal Muscle

Abstract

Different genetic and imaging iron markers are known to be increased in the liver, adipose tissue, and brain of obese subjects. We aimed to investigate these markers in human skeletal muscle. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: Markers of iron accumulation were measured in three different territories: Iron gene markers (TFRC1, TF, SLC11A2, FTL, FTH1, and SLC40A1) were studied in abdominal rectus abdominis (Cohort 1, n = 26) and quadriceps (Cohort 2, n = 13) muscle using real-time PCR, whereas paravertebral muscle R2* signal (as surrogate of iron content) (Cohort 3, n = 43) was evaluated by means of magnetic resonance imaging. In a subgroup of 14 obese participants from Cohort 3, a diet-induced weight loss was performed. Rectus abdominis muscle age-adjusted gene expression of SLC40A1 (ferroportin) (r = 0.47; P = .04), SLC11A2 (r = 0.50; P = .03) and CYBA (r = 0.62; P = .006) increased with body fatness. In obese participants from Cohort 1, muscle CYBA gene expression was positively correlated with serum ferritin. This association was replicated in quadriceps from obese participants (Cohort 2). Paravertebral muscle R2* was positively associated with body mass index, waist circumference, and fat mass (measured by dual-energy x-ray absorptiometry) in parallel with hepatic iron content, serum ferritin, and hepcidin. In multivariate regression analyses, obesity parameters (P < .0001) and hsCRP concentration (P < .05) contributed independently to the variance of sex-, serum hepcidin- and age-adjusted muscle R2*. Of note, weight loss intervention resulted in decreased muscle R2* (P = .02) in correlation with the change of serum ferritin (r = 0.69; P = .01). These findings emphasize a significant iron accumulation in human skeletal muscle in association with obesity. The mechanisms implicated in these observations should be studied further.