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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.
Afiliación
  • Nazari M; Centre for Diabetes, Obesity and Endocrinology (CDOE), The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia.
  • Ho KW; Faculty of Medicine and Health, The University of Sydney, Westmead, Australia.
  • Langley N; Faculty of Medicine and Health, The University of Sydney, Westmead, Australia.
  • Cha KM; Garvan Institute of Medical Research, Darlinghurst Sydney, Australia.
  • Kodsi R; Centre for Diabetes, Obesity and Endocrinology (CDOE), The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia.
  • Wang M; Centre for Diabetes, Obesity and Endocrinology (CDOE), The Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW, 2145, Australia.
  • Laybutt DR; Garvan Institute of Medical Research, Darlinghurst Sydney, Australia.
  • Cheng K; Garvan Institute of Medical Research, Darlinghurst Sydney, Australia.
  • Stokes RA; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, Australia.
  • Swarbrick MM; Garvan Institute of Medical Research, Darlinghurst Sydney, Australia.
  • Gunton JE; Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, Australia.
Sci Rep ; 12(1): 776, 2022 01 14.
Article en En | MEDLINE | ID: mdl-35031684
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Quelantes del Hierro / Tejido Adiposo Beige / Deferasirox / Obesidad Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diferenciación Celular / Quelantes del Hierro / Tejido Adiposo Beige / Deferasirox / Obesidad Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido