Skeletal muscle ferritin abundance is tightly related to plasma ferritin concentration in adults with obesity

New findings What is the central question of this study? Obesity is associated with complex perturbations to iron homeostasis: is plasma ferritin concentration (a biomarker of whole-body iron stores) related to the abundance of ferritin (the key tissue iron storage protein) in skeletal muscle in adults with obesity? What is the main finding and its importance? Plasma ferritin concentration was tightly correlated with the abundance of ferritin in skeletal muscle, and this relationship persisted when accounting for sex, age, body mass index and plasma C-reactive protein concentration. Our findings suggest that skeletal muscle may be an important iron store. Abstract Obesity is associated with complex perturbations to whole-body and tissue iron homeostasis. Recent evidence suggests a potentially important influence of iron storage in skeletal muscle on whole-body iron homeostasis, but this association is not clearly resolved. The primary aim of this study was to assess the relationship between whole-body and skeletal muscle iron stores by measuring the abundance of the key iron storage (ferritin) and import (transferrin receptor) proteins in skeletal muscle, as well as markers of whole-body iron homeostasis in men (n = 19) and women (n = 43) with obesity. Plasma ferritin concentration (a marker of whole-body iron stores) was highly correlated with muscle ferritin abundance (r = 0.77, P = 2 × 10-13 ) and negatively associated with muscle transferrin receptor abundance (r = -0.76, P = 1 × 10-12 ). These relationships persisted when accounting for sex, age, BMI and plasma C-reactive protein concentration. In parallel with higher whole-body iron stores in our male versus female participants, men had 2.2-fold higher muscle ferritin abundance (P = 1 × 10-4 ) compared with women. In accordance with lower muscle iron storage, women had 2.7-fold higher transferrin receptor abundance (P = 7 × 10-10 ) compared with men. We conclude that muscle iron storage and import proteins are tightly and independently related to plasma ferritin concentration in adults with obesity, suggesting that skeletal muscle may be an underappreciated iron store.