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.

Deregulating the CYP2C19/Epoxy-Eicosatrienoic Acid-Associated FABP4/FABP5 Signaling Network as a Therapeutic Approach for Metastatic Triple-Negative Breast Cancer

“…To investigate whether cells present in the tumor microenvironment can influence metastatic TNBC cell behavior and expression of CYP2C19, FABP4, and FABP5, we used an in vitro co-culture model, selecting some of the representative tumor stromal cells, namely fibroblasts, adipocytes, and cells of monocytic lineage known to influence lipid homeostasis in breast cancer cells [8,[43][44][45][46]. Prior to co-culture with TNBC cells, first, we examined the adipogenic markers in undifferentiated fibroblasts (3T3-L1), a stable adipocyte differentiated cell line derived from 3T3-L1 (3T3-adipocytes); an undifferentiated monocytic cell line (THP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), which regulates adipocyte differentiation; CCAAT/enhancer binding protein α (C/EBPα) which is responsible for mitotic growth arrest and late-stage adipocyte differentiation; and FABP4, FABP5, and CYP2C19 in the THP-1 and 3T3-L1 cells.…”

RNA‐Seq analysis reveals the potential molecular mechanisms of daidzein on adipogenesis in subcutaneous adipose tissue of finishing Xianan beef cattle

“…The present results showed that daidzein significantly upregulated the expression level of FABP7 and ELOVL genes and significantly downregulated the expression level of GPR41 and SCD genes. FABP7 gene is a member of fatty acid-binding protein family and played an important role in the uptake of long-chain fatty acid in cytomembrane (Yamamoto et al, 2016). ELOVL gene could elongate the long-chain fatty acid in adipocytes (Harkewicz et al, 2012).…”

Comparative Analysis of Human Adipose-Derived Mesenchymal Stem Cells from Orbital and Abdominal Fat

“…It is reported that FABP4 is an adipokine with a distinct role of transcriptional and metabolic regulation in ASCs [45]. In this study, ORO staining results showed that both ASCs were induced when cultured in adipogenic medium and orbital ASCs have more adipogenic property compared to abdominal ASCs, which was ascertained by mRNA expressions of genes involved in adipogenesis.…”