IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway

J Invest Dermatol. 2008 May;128(5):1286-93. doi: 10.1038/sj.jid.5701155. Epub 2007 Nov 8.


Understanding the factors that regulate sebum production is important in identifying therapeutic targets for acne therapy. Insulin and IGF-1 stimulate sebaceous gland lipogenesis. IGF-1 increases expression of sterol response element-binding protein-1 (SREBP-1), a transcription factor that regulates numerous genes involved in lipid biosynthesis. SREBP-1 expression, in turn, stimulates lipogenesis in sebocytes. The goal of this study was to identify the intracellular signaling pathway(s) that transduces the lipogenic signal initiated by IGF-1. Sebocytes were treated with IGF-1 and assayed for activation of the phosphoinositide 3-kinase (PI3-K) pathway and of the three major arms of the mitogen-activated protein kinase (MAPK) pathway (MAPK/extracellular signal-regulated kinase (ERK), p38 MAPK, and stress-activated protein kinase/c-Jun-N terminal kinase). IGF-1 activated the MAPK/ERK and PI-3K pathways. Using specific inhibitors of each pathway, we found that the increase in expression of SREBP-1 induced by IGF-1 was blocked in the presence of the PI3-K inhibitor but not in the presence of the MAPK/ERK inhibitor. Furthermore, inhibition of the PI3-K pathway also blocked the IGF-1-induced transcription of SREBP target genes and sebocyte lipogenesis. These data indicate that IGF-1 transmits its lipogenic signal in sebocytes through activation of Akt. Specific targeted interruption of this pathway in the sebaceous gland could be a desirable approach to reducing sebum production and improving acne.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acne Vulgaris / metabolism
  • Cell Line, Transformed
  • Chromones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Humans
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipogenesis / drug effects*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Sebaceous Glands / cytology
  • Sebaceous Glands / enzymology*
  • Sebum / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics*
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Chromones
  • Enzyme Inhibitors
  • Flavonoids
  • Morpholines
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one