Abstract
Excess adipogenesis is a characteristic of obesity, which is associated with serious health problem, including type 2 diabetes. Here, to better understand the mechanisms for the development of adipocytes, we investigated the regulatory role of 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in adipogenesis by treating 3T3-L1 murine preadipocytes and human bone marrow mesenchymal stem cells (hBMSCs) with 15(S)-HETE. In the 3T3-L1 study, 15(S)-HETE stimulated lipid accumulation and enhanced expression of adipogenic markers such as peroxisome proliferator-activated receptor gamma (PPARγ), yet reduced the activity of factor negatively controlling adipogenesis, such as the 5'-AMP-activated protein kinase. In the early stage of adipogenesis, 15(S)-HETE increased activation of protein kinase B and expression of CCAAT/enhancer-binding protein (C/EBP)β and C/EBPδ. Finally, 15(S)-HETE promoted adipogenesis in hBMSCs, and resulted in increased lipid accumulation and expression of adipogenic markers. In conclusion, 15(S)-HETE functions as a natural PPARγ agonist and enhances adipogenesis. Our findings may provide the basis for the development of novel therapeutic measures to treat obesity.
Keywords:
15-(S)-hydroxyeicosatetraenoic acid; 3T3-L1; Adipogenesis; Obesity; PPARγ; hBMSC.
Copyright © 2016 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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AMP-Activated Protein Kinases / genetics
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AMP-Activated Protein Kinases / metabolism
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Adipocytes / cytology
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Adipocytes / drug effects*
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Adipocytes / metabolism
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Adipogenesis / drug effects*
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Adipogenesis / genetics
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Animals
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Arachidonate 12-Lipoxygenase / genetics
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Arachidonate 12-Lipoxygenase / metabolism
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Arachidonate 15-Lipoxygenase / genetics
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Arachidonate 15-Lipoxygenase / metabolism
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CCAAT-Enhancer-Binding Protein-beta / genetics
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CCAAT-Enhancer-Binding Protein-beta / metabolism
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CCAAT-Enhancer-Binding Protein-delta / genetics
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CCAAT-Enhancer-Binding Protein-delta / metabolism
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Cell Differentiation / drug effects
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Cells, Cultured
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Gene Expression Regulation
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Humans
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Hydroxyeicosatetraenoic Acids / pharmacology*
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / drug effects*
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Mesenchymal Stem Cells / metabolism
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Mice
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PPAR gamma / agonists*
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PPAR gamma / genetics
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PPAR gamma / metabolism
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction
Substances
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12-15-lipoxygenase
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CCAAT-Enhancer-Binding Protein-beta
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CEBPB protein, human
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CEBPD protein, human
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Hydroxyeicosatetraenoic Acids
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PPAR gamma
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CCAAT-Enhancer-Binding Protein-delta
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15-hydroxy-5,8,11,13-eicosatetraenoic acid
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Arachidonate 12-Lipoxygenase
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Arachidonate 15-Lipoxygenase
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Proto-Oncogene Proteins c-akt
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AMP-Activated Protein Kinases