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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. Strat...

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Autores principales: Nazari, Mojgan, Ho, Kenneth W., Langley, Natasha, Cha, Kuan M., Kodsi, Raymond, Wang, Mawson, Laybutt, D. Ross, Cheng, Kim, Stokes, Rebecca A., Swarbrick, Michael M., Gunton, Jenny E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760280/
https://www.ncbi.nlm.nih.gov/pubmed/35031684
http://dx.doi.org/10.1038/s41598-022-04809-8
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author Nazari, Mojgan
Ho, Kenneth W.
Langley, Natasha
Cha, Kuan M.
Kodsi, Raymond
Wang, Mawson
Laybutt, D. Ross
Cheng, Kim
Stokes, Rebecca A.
Swarbrick, Michael M.
Gunton, Jenny E.
author_facet Nazari, Mojgan
Ho, Kenneth W.
Langley, Natasha
Cha, Kuan M.
Kodsi, Raymond
Wang, Mawson
Laybutt, D. Ross
Cheng, Kim
Stokes, Rebecca A.
Swarbrick, Michael M.
Gunton, Jenny E.
author_sort Nazari, Mojgan
collection PubMed
description 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.
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spelling pubmed-87602802022-01-18 Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity Nazari, Mojgan Ho, Kenneth W. Langley, Natasha Cha, Kuan M. Kodsi, Raymond Wang, Mawson Laybutt, D. Ross Cheng, Kim Stokes, Rebecca A. Swarbrick, Michael M. Gunton, Jenny E. Sci Rep Article 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. Nature Publishing Group UK 2022-01-14 /pmc/articles/PMC8760280/ /pubmed/35031684 http://dx.doi.org/10.1038/s41598-022-04809-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Nazari, Mojgan
Ho, Kenneth W.
Langley, Natasha
Cha, Kuan M.
Kodsi, Raymond
Wang, Mawson
Laybutt, D. Ross
Cheng, Kim
Stokes, Rebecca A.
Swarbrick, Michael M.
Gunton, Jenny E.
Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity
title Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity
title_full Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity
title_fullStr Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity
title_full_unstemmed Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity
title_short Iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity
title_sort iron chelation increases beige fat differentiation and metabolic activity, preventing and treating obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760280/
https://www.ncbi.nlm.nih.gov/pubmed/35031684
http://dx.doi.org/10.1038/s41598-022-04809-8
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