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Heparin-binding epidermal growth factor-like growth factor inhibits adipocyte differentiation at commitment and early induction stages.

 Jeong Soon Lee  ;  Jae Myoung Suh  ;  Hong Gyu Park  ;  Eun Jung Bak  ;  Yun-Jung Yoo  ;  Jeong-Heon Cha 
 DIFFERENTIATION, Vol.76(5) : 478-487, 2008 
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1-Methyl-3-isobutylxanthine/pharmacology ; Adipocytes/cytology* ; Adipogenesis/drug effects* ; Adipogenesis/physiology ; Animals ; Bone Morphogenetic Proteins/pharmacology ; Cell Differentiation/drug effects ; Cell Line/drug effects ; Cell Lineage ; Depression, Chemical ; Dexamethasone/pharmacology ; Fibroblasts/cytology ; Fibroblasts/drug effects* ; Fibroblasts/metabolism ; Gene Expression Profiling ; Gene Expression Regulation/drug effects* ; Heparin-binding EGF-like Growth Factor ; Humans ; Insulin/pharmacology ; Intercellular Signaling Peptides and Proteins/biosynthesis ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/pharmacology* ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/drug effects ; Mesenchymal Stromal Cells/metabolism ; Mice ; Mice, Inbred C3H ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics
HB-EGF ; BMP4 ; C3H10T1/2 ; mesenchymal stem cell ; adipocyte differentiation ; EGF receptor ; mitotic clonal expansion ; C/EBPα ; PPARγ ; aP2
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 gamma, and CAAT enhancer-binding protein alpha) 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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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Hong Gyu(박홍규)
Yoo, Yun Jung(유윤정) ORCID logo https://orcid.org/0000-0002-0045-9597
Lee, Jeong Soon(이정순)
Cha, Jeong Heon(차정헌) ORCID logo https://orcid.org/0000-0002-9385-2653
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