Heparin-binding epidermal growth factor-like growth factor inhibits adipocyte differentiation at commitment and early induction stages.
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.
Lee
Jeong Soon
JS
Department of Oral Biology, BK21 Project, Oral Science Research Center, Yonsei University College of Dentistry, Seoul 120-752, Korea.
Suh
Jae Myoung
JM
Park
Hong Gyu
HG
Bak
Eun Jung
EJ
Yoo
Yun-Jung
YJ
Cha
Jeong-Heon
JH
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
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