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.
|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|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/35031684|