Metabolic programming of a beige adipocyte phenotype by genistein.
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.



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.



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.
Institute for Cell and Molecular Biosciences, Newcastle upon Tyne, UK.
Sadat A
SA
Aziz
School of Dental Sciences, Newcastle University, Newcastle upon Tyne, UK.
Luisa A
LA
Wakeling
Institute for Cell and Molecular Biosciences, Newcastle upon Tyne, UK.
Satomi
S
Miwa
Department of Obstetrics and Gynaecology, University College Dublin, Dublin, UK.
Goiuri
G
Alberdi
Institute for Cell and Molecular Biosciences, Newcastle upon Tyne, UK.
John E
JE
Hesketh
Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
Dianne
D
Ford
D041721:3T3-L1 Cells; D000069797:Adipocytes, Beige / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D051379:Mice; D011960:Receptors, Estrogen / Q000378:metabolism
C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D002227:Carbazoles; D011960:Receptors, Estrogen; D019833:Genistein
Brown adipose tissue; Estrogen receptor; Genistein; SIRT1; White adipose tissue
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