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Publication : Fam57b (family with sequence similarity 57, member B), a novel peroxisome proliferator-activated receptor γ target gene that regulates adipogenesis through ceramide synthesis.

First Author  Yamashita-Sugahara Y Year  2013
Journal  J Biol Chem Volume  288
Issue  7 Pages  4522-37
PubMed ID  23275342 Mgi Jnum  J:197105
Mgi Id  MGI:5490837 Doi  10.1074/jbc.M112.440792
Citation  Yamashita-Sugahara Y, et al. (2013) Fam57b (family with sequence similarity 57, member B), a novel peroxisome proliferator-activated receptor gamma target gene that regulates adipogenesis through ceramide synthesis. J Biol Chem 288(7):4522-37
abstractText  This report identifies a novel gene encoding Fam57b (family with sequence similarity 57, member B) as a novel peroxisome proliferator-activated receptor gamma (PPARgamma)-responsive transmembrane gene that is related to obesity. The gene was identified based on an integrated bioinformatics analysis of the following three expression profiling data sets: adipocyte differentiation of mouse stromal cells (ST2 cells), adipose tissues from obesity mice, and siRNA-mediated knockdown of Ppargamma using ST2 cells. Fam57b consists of three variants expressed from different promoters and contains a Tram-Lag1-CLN8 domain that is related to ceramide synthase. Reporter and ChIP assays showed that Fam57b variant 2 is a bona fide PPARgamma target gene in ST2 cells. Fam57b was up-regulated during adipocyte differentiation, suggesting that FAM57B is involved in this process. Surprisingly, FAM57B overexpression inhibited adipogenesis, and siRNA-mediated knockdown promoted adipocyte differentiation. Analysis of the ceramide content by lipid assay found that ceramides were in fact augmented in FAM57B-overexpressing ST2 cells. We also confirmed that ceramide inhibits adipogenesis. Therefore, the aforementioned results of FAM57B overexpression and siRNA experiments are reconciled by ceramide synthesis. In summary, we present in vitro evidence showing that PPARgamma regulates Fam57b transcription during the adipogenesis of ST2 cells. In addition, our results suggest that PPARgamma activation contributes to the regulation of ceramide metabolism during adipogenesis via FAM57B.
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