Scientific Reports (Jan 2022)

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

  • Mojgan Nazari,
  • Kenneth W. Ho,
  • Natasha Langley,
  • Kuan M. Cha,
  • Raymond Kodsi,
  • Mawson Wang,
  • D. Ross Laybutt,
  • Kim Cheng,
  • Rebecca A. Stokes,
  • Michael M. Swarbrick,
  • Jenny E. Gunton

DOI
https://doi.org/10.1038/s41598-022-04809-8
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 11

Abstract

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Abstract 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.