期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 61, 期 2, 页码 -出版社
WILEY
DOI: 10.1002/mnfr.201600574
关键词
Brown adipose tissue; Estrogen receptor; Genistein; SIRT1; White adipose tissue
资金
- UK Biotechnology and Biological Sciences Research Council (BBSRC) [BBE0074571]
- Ministry of Higher Education and Scientific Research, Kurdistan Regional Government, Iraq
ScopePromoting 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 resultsWe 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 (Cebp, Pgc1, 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 Cebp 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. ConclusionsWe 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.
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