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Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity


Beige and brown fat consume glucose and lipids to produce heat, using uncoupling protein 1 (UCP1). It is thought that full activation of brown adipose tissue (BAT) may increase total daily energy expenditure by 20%. Humans normally have more beige and potentially beige-able fat than brown fat. Strategies to increase beige fat differentiation and activation may be useful for the treatment of obesity and diabetes. Mice were fed chow or high-fat diet (HFD) with or without the iron chelator deferasirox. Animals fed HFD + deferasirox were markedly lighter than their HFD controls with increased energy expenditure (12% increase over 24 h, p < 0.001). Inguinal fat from HFD + deferasirox mice showed increased beige fat quantity with greater Ucp1 and Prdm16 expression. Inguinal adipose tissue explants were studied in a Seahorse bioanalyser and energy expenditure was significantly increased. Deferasirox was also effective in established obesity and in ob/ob mice, indicating that intact leptin signalling is not needed for efficacy. These studies identify iron chelation as a strategy to preferentially activate beige fat. Whether activating brown/beige fat is effective in humans is unproven. However, depleting iron to low-normal levels is a potential therapeutic strategy to improve obesity and related metabolic disorders, and human studies may be warranted.

Type Journal
ISBN 2045-2322 (Electronic) 2045-2322 (Linking)
Authors Nazari, M.; Ho, K. W.; Langley, N.; Cha, K. M.; Kodsi, R.; Wang, M.; Laybutt, D. R.; Cheng, K.; Stokes, R. A.; Swarbrick, M. M.; Gunton, J. E.
Publisher Name Scientific Reports
Published Date 2022-01-14
Published Volume 12
Published Issue 1
Published Pages 776
Status Published in-print
DOI 10.1038/s41598-022-04809-8
URL link to publisher's version