Insulin-like growth factor-I stimulates both cell growth and lipogenesis during differentiation of human mesenchymal stem cells into adipocytes.
Insulin is known to regulate adipocyte differentiation and lipid accumulation, but the specific mechanism by which precursor cells differentiate into adipocytes is not clearly understood. This study evaluated the role of the IGF-I receptor in the process of adipocyte differentiation in bone marrow-derived human mesenchymal stem cells (HMSCs). The results demonstrated that nanomolar concentrations of IGF-I adequately replaced micromolar concentrations of insulin in supporting differentiation and lipid accumulation in HMSCs. The addition of IGF-I specifically increased cell proliferation and lipid accumulation in HMSCs, but a mixture of differentiation factors including dexamethasone, indomethacin, and 3-isobutyl-1-methylxanthine did not. These effects were blocked by the alphaIR-3 antibody, which inhibits IGF-I receptor activity. We also describe the pattern of differentiation with regard to cell growth, lipid accumulation, and morphologic changes and define the changes in these parameters that are influenced by IGF-I. Finally, peroxisome proliferator activating receptor-gamma immunoreactivity was also increased in response to IGF-I, and this effect was blocked in cells treated with the alphaIR-3 antibody. Taken together, these findings suggest that IGF-I plays a critical role in adipocyte differentiation and lipid accumulation.
Scavo
Louis M
LM
Division of Neonatology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC 20010, USA.
Karas
Michael
M
Murray
Malissa
M
Leroith
Derek
D
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D000906:Antibodies; D008055:Lipids; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt