title: 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, 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.
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
authors.forename: Petar D
authors.initials: PD
authors.lastname: Petrov
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
authors.forename: Andreu
authors.initials: A
authors.lastname: Palou
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Bonet
authors.affiliation: Laboratory of Molecular Biology, Nutrition and Biotechnology-Nutrigenomics, Universitat de les Illes Balears, Palma de Mallorca, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Ribot
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D016161:Genes, Retinoblastoma / Q000235:genetics; D006239:Haplotypes; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism; D010641:Phenotype; D012175:Retinoblastoma / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D022722:Thermogenesis; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016160:Retinoblastoma Protein; D014157:Transcription Factors