RRC ID 29212
Author Yamashita-Sugahara Y, Tokuzawa Y, Nakachi Y, Kanesaki-Yatsuka Y, Matsumoto M, Mizuno Y, Okazaki Y.
Title Fam57b (family with sequence similarity 57, member B), a novel peroxisome proliferator-activated receptor γ target gene that regulates adipogenesis through ceramide synthesis.
Journal J Biol Chem
Abstract This report identifies a novel gene encoding Fam57b (family with sequence similarity 57, member B) as a novel peroxisome proliferator-activated receptor γ (PPARγ)-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 Pparγ 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 PPARγ 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 PPARγ regulates Fam57b transcription during the adipogenesis of ST2 cells. In addition, our results suggest that PPARγ activation contributes to the regulation of ceramide metabolism during adipogenesis via FAM57B.
Volume 288(7)
Pages 4522-37
Published 2013-2-15
DOI 10.1074/jbc.M112.440792
PII S0021-9258(20)46257-X
PMID 23275342
PMC PMC3576059
MeSH 3T3 Cells Adipocytes / cytology* Adipogenesis Animals Base Sequence Cell Differentiation Ceramides / metabolism* Diet, High-Fat Disease Models, Animal Gene Expression Regulation* Membrane Proteins / metabolism* Metabolic Syndrome / genetics Mice Molecular Sequence Data Obesity / genetics Obesity / metabolism* Oligonucleotide Array Sequence Analysis PPAR gamma / metabolism* RNA, Small Interfering / metabolism Sequence Homology, Nucleic Acid Signal Transduction Sphingolipids / metabolism Sphingosine N-Acyltransferase / biosynthesis* Sphingosine N-Acyltransferase / genetics Stromal Cells / cytology
IF 4.238
Times Cited 13
DNA material pGCDNsam-Fam57b_var1-IRES-EGFP(IG) (RDB12135) pGCDNsam-Fam57b_var1FLAG-IG (RDB12136) pGCDNsam-Fam57b_var2-IG (RDB12137) pGCDNsam-Fam57b_var2FLAG-IG (RDB12138) pGCDNsam-Fam57b_var3-IG (RDB12139) pGCDNsam-Fam57b_var3FLAG-IG (RDB12140)
Human and Animal Cells ST2(RCB0224)