title: Heparin-binding epidermal growth factor-like growth factor inhibits adipocyte differentiation at commitment and early induction stages.
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 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.
authors: Department of Oral Biology, BK21 Project, Oral Science Research Center, Yonsei University College of Dentistry, Seoul 120-752, Korea.
authors: Jeong Soon
authors: JS
authors: Lee
authors: Jae Myoung
authors: JM
authors: Suh
authors: Hong Gyu
authors: HG
authors: Park
authors: Eun Jung
authors: EJ
authors: Bak
authors: Yun-Jung
authors: YJ
authors: Yoo
authors: Jeong-Heon
authors: JH
authors: Cha
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D019070:Cell Lineage; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine