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Metabolic programming of a beige adipocyte phenotype by genistein

Lookup NU author(s): Sadat Aziz, Dr Luisa Wakeling, Dr Satomi Miwa, Goiuri Alberdi Aresti, Professor John Hesketh, Professor Dianne Ford

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2016 The Authors. Molecular Nutrition & Food Research Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Scope: Promoting the development of brown or beige adipose tissue may protect against obesity and related metabolic features, and potentially underlies protective effects of genistein in mice. Methods and results: We observed that application of genistein to 3T3-L1 adipocytes changed the lipid distribution from large droplets to a multilocular distribution, reduced mRNAs indicative of white adipocytes (ACC, Fasn, Fabp4, HSL, chemerin, and resistin) and increased mRNAs that are a characteristic feature of brown/beige adipocytes (CD-137 and UCP1). Transcripts with a role in adipocyte differentiation (Cebpβ, Pgc1α, Sirt1) peaked at different times after application of genistein. These responses were not affected by the estrogen receptor (ER) antagonist fulvestrant, revealing that this action of genistein is not through the classical ER pathway. The Sirt1 inhibitor Ex-527 curtailed the genistein-mediated increase in UCP1 and Cebpβ mRNA, revealing a role for Sirt1 in mediating the effect. Baseline oxygen consumption and the proportional contribution of proton leak to maximal respiratory capacity was greater for cells exposed to genistein, demonstrating greater mitochondrial uncoupling. Conclusions: We conclude that genistein acts directly on adipocytes or on adipocyte progenitor cells to programme the cells metabolically to adopt features of beige adipocytes. Thus, this natural dietary agent may protect against obesity and related metabolic disease.


Publication metadata

Author(s): Aziz SA, Wakeling LA, Miwa S, Alberdi G, Hesketh JE, Ford D

Publication type: Article

Publication status: Published

Journal: Molecular Nutrition and Food Research

Year: 2017

Volume: 61

Issue: 2

Print publication date: 01/02/2017

Online publication date: 27/09/2016

Acceptance date: 11/09/2016

Date deposited: 20/04/2017

ISSN (print): 1613-4125

ISSN (electronic): 1613-4133

Publisher: Wiley-VCH Verlag

URL: https://doi.org/10.1002/mnfr.201600574

DOI: 10.1002/mnfr.201600574


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