Heparin-binding epidermal growth factor-like growth factor inhibits adipocyte differentiation at commitment and early induction stages |
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Authors: | Lee Jeong Soon Suh Jae Myoung Park Hong Gyu Bak Eun Jung Yoo Yun-Jung Cha Jeong-Heon |
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Affiliation: | Department of Oral Biology, BK21 Project, Oral Science Research Center, Yonsei University College of Dentistry, Seoul 120-752, Korea Tel: +82 2 2228 3061 Fax: +82 2 2227 7903; Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, Korea |
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Abstract: | Abstract Adipocytokines, bioactive molecules secreted from adipose tissues, play important roles in physiology, development, and disease. Recently, heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified as an adipocytokine whose expression correlates with obesity. However, the biological role of fat-secreted HB-EGF is still unclear. In this study, we investigated the effects of HB-EGF on the adipocyte differentiation of C3H10T1/2 pluripotent mesenchymal cells. Upon adipogenic conversion of C3H10T1/2 cells, HB-EGF displayed dynamic changes in expression where an initial decrease was followed by increased levels of expression at later stages. HB-EGF treatment during adipogenic induction inhibited lipid accumulation and decreased the expression of adipocyte molecular markers (fatty acid-binding protein, peroxisome proliferator-activated receptor γ, and CAAT enhancer-binding protein α) and lipogenic genes (glucose transporter, fatty acid synthetase, and lipoprotein lipase). Therefore, HB-EGF has an inhibitory effect on adipocyte differentiation. Administration of HB-EGF at various intervals during adipocyte differentiation revealed that HB-EGF acts during the early stages of adipocyte differentiation, but not at the later stages of differentiation. Furthermore, HB-EGF was able to block the commitment of pluripotent mesenchymal cells to the adipocyte lineage triggered by bone morphogenic protein 4 treatment. These data suggest that HB-EGF acts as a negative regulator of adipogenesis by inhibiting the commitment and early differentiation of the adipose lineage. The inhibitory role of HB-EGF on adipocyte differentiation of pluripotent mesenchymal cells sheds light on potential mechanisms that control adipose tissue homeostasis. |
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Keywords: | HB-EGF BMP4 C3H10T1/2 mesenchymal stem cell adipocyte differentiation EGF receptor mitotic clonal expansion C/EBPα PPARγ aP2 |
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