title: Fam57b (family with sequence similarity 57, member B), a novel peroxisome proliferator-activated receptor γ target gene that regulates adipogenesis through ceramide synthesis.
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.
authors.affiliation: Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1241, Japan.
authors.forename: Yzumi
authors.initials: Y
authors.lastname: Yamashita-Sugahara
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Tokuzawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakachi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanesaki-Yatsuka
authors.forename: Masahito
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002518:Ceramides / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism; D051049:Sphingosine N-Acyltransferase / Q000096:biosynthesis* / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology
chemical_list: D002518:Ceramides; D008565:Membrane Proteins; D047495:PPAR gamma; D034741:RNA, Small Interfering; D013107:Sphingolipids; C580718:FAM57B protein, mouse; D051049:Sphingosine N-Acyltransferase