IGF-1 Induces SREBP-1 Expression and Lipogenesis in SEB-1 Sebocytes via Activation of the Phosphoinositide 3-Kinase/Akt Pathway

The Jake Gittlen Cancer Research Foundation, Hershey, Pennsylvania, USA.
Journal of Investigative Dermatology (Impact Factor: 7.22). 06/2008; 128(5):1286-93. DOI: 10.1038/sj.jid.5701155
Source: PubMed


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.

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    • "The effect of IGF-1 on lipogenesis in hepatocytes has not been investigated, but there is evidence that IGF-1 regulates lipogenesis in other tissues. In 2008, it was shown that IGF-1 regulates SREBP-1 expression and lipogenesis in sebocytes— cells derived from the sebaceous gland—through a PI3K dependent pathway (Smith et al . 2008). It is logical that since the liver is also responsive to IGF-1, lipogenesis would likewise be activated. Insulin and IGF-1 can both stimulate glycogen synthesis in hepatocytes (Park et al. 1999). While glycogenesis and lipogenesis are distinct pathways, recent work has shown that they are coordinately regulated processes, and it was r"
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