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Mechanisms behind the emergence of brown adipocyte-like (brite or beige) adipocytes within white adipose tissue (WAT) are of interest. Retinoblastoma protein gene (Rb) haploinsufficiency associates in mice with improved metabolic regulation linked to a greater capacity for fatty acid oxidation and thermogenesis in WAT. We aimed to explain a feasible mechanism of WAT-to-BAT remodeling in this model. Differentiated primary adipocytes and Sca1-positive preadipocytes derived from adipose depots of Rb+/- mice and wild-type siblings were compared. Primary white Rb+/- adipocytes displayed under basal conditions increased glucose uptake and an enhanced expression of brown adipocyte-related genes (Pparg, Ppargc1a, Ppargc1b, Prdm16, Cpt1b) but not of purported beige/brite transcriptional markers (Cd137, Tmem26, Tbx1, Slc27a1, Hoxc9, Shox2). Lack of induction of beige markers phenocopied results in WAT of adult Rb+/- mice. Flow cytometry analysis evidenced an increased number of preadipocytes in WAT depots of Rb+/- mice. Sca1(+) preadipocytes from WAT of Rb+/- mice displayed increased gene expression of several transcription factors common to the brown and beige adipogenic programs (Prdm16, Pparg, Ppargc1a) and of receptors of bone morphogenetic proteins (BMPs); however, among the recently proposed beige markers, only Tbx1 was upregulated. Adult Rb+/- mice had increased circulating levels of BMP7. These results indicate that preadipose cells resident in WAT depots of Rb+/- mice retain an increased capacity for brown-like adipogenesis that appears to be different from beige adipogenesis, and suggest that the contribution of these precursors to the Rb+/- adipose phenotype is driven, at least in part, by interaction with BMP7 pathways. (C) 2016 Wiley Periodicals, Inc.

White adipose tissue (WAT) can differentiate into beige adipose tissue by the browning process. Some polyphenols, including isoflavones, particularly genistein, are suggested to increase the expression of browning markers. There is evidence that consumption of genistein can attenuate body weight gain and improve glucose tolerance and blood lipid levels. The aim of the present study was to investigate the potential mechanisms of stimulation by which genistein activates the browning of WAT. We studied the stimulation of the expression of browning markers in the following models: mice fed genistein; preadipocytes from 3 T3-L1 cells; and the stromal vascular fraction (SVF) from the inguinal adipose tissue of mice. The results indicated that genistein can stimulate the browning process by at least two mechanisms. An indirect mechanism was involved in the induction of PGC-1 alpha/FNDC5 in skeletal muscle leading to an increase in the myokine irisin. In preadipocytes, irisin was able to increase the expression of Ucpl and Tmem26, markers of browning, to increase energy expenditure. Interestingly, genistein was also able to activate browning by a direct mechanism. Incubation of preadipocytes with genistein increased UCP1 expression as well as some biomarkers of browning in a concentration-dependent manner, possibly via phosphorylation of AMPK. The effect of genistein was accompanied by an increase in the number of mitochondria as well as in the maximum respiration rate of the adipocytes. In conclusion, this study indicated that genistein can increase energy expenditure by stimulating the browning process directly in preadipocytes and indirectly by increasing the circulating levels of irisin. (C) 2019 Elsevier Inc. All rights reserved.