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Cell‐Autonomous Brown‐Like Adipogenesis of Preadipocytes From Retinoblastoma Haploinsufficient Mice
Author(s) -
Petrov Petar D.,
Palou Andreu,
Bonet M. Luisa,
Ribot Joan
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25299
Subject(s) - prdm16 , adipogenesis , peroxisome proliferator activated receptor gamma , white adipose tissue , medicine , endocrinology , biology , thermogenesis , thermogenin , adipose tissue , adipocyte , microbiology and biotechnology , peroxisome proliferator activated receptor , receptor
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. J. Cell. Physiol. 231: 1941–1952, 2016. © 2016 Wiley Periodicals, Inc.