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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)478-487
Number of pages10
JournalDifferentiation
Volume76
Issue number5
DOIs
Publication statusPublished - 2008 Jun

Bibliographical note

Funding Information:
Acknowledgments We thank Jae Bum Kim for providing 3T3-F442A cells. Also, we thank Jang Gi Cho for help with graphics, and Sang-Kyu Park, So Young Kim, and Jin Hee Park for technical assistance. This work was supported by KOREA Research Foundation Grant (KRF-2003-015-E00182).

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology
  • Cancer Research

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