Cell-Autonomous Brown-Like Adipogenesis of Preadipocytes from Retinoblastoma Haploinsufficient Mice

Abstract

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, amongst 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. This article is protected by copyright. All rights reserved

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from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1OJewIG
via IFTTT