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.
Highlights
Mesenchymal stem cells are multipotent somatic stem cells that can differentiate into a variety of cell types such as adipocytes, osteoblasts, chondrocytes and myocytes [1]
Since little is known about paracrine roles of Fatty acid-binding protein 4 (FABP4) and FABP5 derived from adipocytes in adipose-derived stem cells (ADSC), we investigated whether exogenous FABP4 and FABP5
FABP4 was not detected in the conditioned medium of ADSC at Day 0 and Day 4 after inducing adipocyte differentiation, but a high concentration of FABP4 was detected at Day 8 (Fig 1A)
Summary
Mesenchymal stem cells are multipotent somatic stem cells that can differentiate into a variety of cell types such as adipocytes, osteoblasts, chondrocytes and myocytes [1]. Mesenchymal stem cells were originally isolated from bone marrow, but they have been isolated from other connective tissues such as adipose tissue, periosteum, synovium and deciduous teeth. A merit of regenerative medicine using autologous mesenchymal stem cells is that immunosuppression is not required. A large number of adipose-derived stem cells (ADSC), which exist near adipocytes in adipose tissue, can be obtained by liposuction, making them more clinically applicable. ADSC have been used clinically as a highly potential tool of regenerative medicine. It has been proposed that intracellular FABPs facilitate the transport of lipids to specific compartments in the cell. We previously showed that inhibition of FABP4 in the cell would be a novel therapeutic strategy against insulin resistance, diabetes mellitus and atherosclerosis [12]
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