title: Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells.
abstract: Adipose-derived stem cells (ADSC), which exist near adipocytes in adipose tissue, have been used as a potential tool of regenerative medicine. Lipid chaperones, fatty acid-binding protein 4 (FABP4) and 5 (FABP5), are abundantly expressed in adipocytes. FABP4 has recently been shown to be secreted from adipocytes during lipolysis in a non-classical pathway and may act as an adipokine. Here, we investigated the role of exogenous FABP4 and FABP5 in transcriptional and metabolic regulation in ADSC. FABP4 and FABP5 were little expressed in ADSC. However, both FABP4 and FABP5 were significantly induced after adipocyte differentiation of ADSC and were secreted from the differentiated adipocytes. Analysis of microarray data, including gene ontology enrichment analysis and cascade analysis of the protein-protein interaction network using a transcription factor binding site search, demonstrated that treatment of ADSC with FABP4 or FABP5 affected several kinds of genes related to inflammatory and metabolic responses and the process of cell differentiation. Notably, myogenic factors, including myocyte enhancer factors, myogenic differentiation 1 and myogenin, were modulated by treatment of ADSC with FABP4, indicating that exogenous FABP4 treatment is partially associated with myogenesis in ADSC. Metabolome analysis showed that treatment of ADSC with FABP4 and with FABP5 similarly, but differently in extent, promoted hydrolysis and/or uptake of lipids, consequentially together with enhancement of β oxidation, inhibition of downstream of the glycolysis pathway, accumulation of amino acids, reduction of nucleic acid components and increase in the ratio of reduced and oxidized nicotinamide adenine dinucleotide phosphates (NADPH/NADP+), an indicator of reducing power, and the ratio of adenosine triphosphate and adenosine monophosphate (ATP/AMP), an indicator of the energy state, in ADSC. In conclusion, secreted FABP4 and FABP5 from adipocytes as adipokines differentially affect transcriptional and metabolic regulation in ADSC near adipocytes. The adiposity condition in the host of regenerative medicine may affect characteristics of ADSC by exposure of the balance of FABP4 and FABP5.
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tokunori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Furuhashi
authors.affiliation: Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Sugao, Miyamae-ku, Kawasaki, Kanagawa, Japan.|CIMIC Co., Ltd; Mass Building Yushima, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sugaya
authors.affiliation: CIMIC Co., Ltd; Mass Building Yushima, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oikawa
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Funahashi
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Matsukawa
authors.affiliation: Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Momokazu
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D055442:Metabolome; D011994:Recombinant Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C493410:FABP4 protein, human; C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D011994:Recombinant Proteins