Plasma ferritin concentration is positively associated with in vivo fatty acid mobilization and insulin resistance in obese women.
Benjamin J RyanDouglas W Van PeltLisa M GuthAlison C LudzkiRachel A Gioscia-RyanChiwoon AhnKatherine L FougJeffrey F HorowitzPublished in: Experimental physiology (2018)
High rates of fatty acid (FA) mobilization from adipose tissue are associated with insulin resistance (IR) in obesity. In vitro evidence suggests that iron stimulates lipolysis in adipocytes, but whether iron is related to in vivo FA mobilization is unknown. We hypothesized that plasma ferritin concentration ([ferritin]), a marker of body iron stores, would be positively associated with FA mobilization. We measured [ferritin], the rate of appearance of FA in the systemic circulation (FA Ra; stable isotope dilution), key adipose tissue lipolytic proteins and IR (hyperinsulinaemic-euglycaemic clamp) in 20 obese, premenopausal women. [Ferritin] was correlated with FA Ra (r = 0.65; P = 0.002) and IR (r = 0.57; P = 0.008); these relationships remained significant after controlling for body mass index and plasma [C-reactive protein] (a marker of systemic inflammation) in multiple regression analyses. We then stratified subjects into tertiles based on [ferritin] to compare subjects with 'High-ferritin' versus 'Low-ferritin'. Plasma [hepcidin] was more than fivefold greater (P < 0.05) in the High-ferritin versus Low-ferritin group, but there was no difference in plasma [C-reactive protein] between groups, indicating that the large difference in plasma [ferritin] reflects a difference in iron stores, not systemic inflammation. We found that FA Ra, adipose protein abundance of hormone-sensitive lipase and adipose triglyceride lipase, and IR were significantly greater in subjects with High-ferritin versus Low-ferritin (all P < 0.05). These data provide the first evidence linking iron and in vivo FA mobilization and suggest that elevated iron stores might contribute to IR in obesity by increasing systemic FA availability.
Keyphrases
- iron deficiency
- adipose tissue
- insulin resistance
- metabolic syndrome
- type diabetes
- high fat diet
- fatty acid
- polycystic ovary syndrome
- weight loss
- high fat diet induced
- skeletal muscle
- machine learning
- pregnant women
- deep learning
- bariatric surgery
- postmenopausal women
- idiopathic pulmonary fibrosis
- glycemic control
- physical activity
- systemic lupus erythematosus
- small molecule
- high resolution
- electronic health record
- liquid chromatography tandem mass spectrometry
- binding protein
- tandem mass spectrometry