Activation of the mTOR pathway enhances PPARγ/SREBP-mediated lipid synthesis in human meibomian gland epithelial cells

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Authors: Ikhyun Jun ; Young Joon Choi ; Bo-Rahm Kim ; Hyung Keun Lee ; Kyoung Yul Seo ; Tae-Im Kim

MeSH: Cell Differentiation / drug effects ; Cells, Cultured ; Epithelial Cells* / drug effects ; Epithelial Cells* / metabolism ; Humans ; Lipid Metabolism ; Lipogenesis* / drug effects ; Mechanistic Target of Rapamycin Complex 1 / metabolism ; Meibomian Glands* / cytology ; Meibomian Glands* / metabolism ; PPAR gamma* / metabolism ; Phosphorylation ; Signal Transduction* ; Sirolimus / pharmacology ; Sterol Regulatory Element Binding Protein 1* / genetics ; Sterol Regulatory Element Binding Protein 1* / metabolism ; TOR Serine-Threonine Kinases* / metabolism

Abstract: The involvement of the mechanistic targets of rapamycin (mTOR) pathway in lipid metabolism has been recently elucidated. However, its specific role in the Meibomian gland, where lipid metabolism is significant, remains not fully understood. We investigated the role of mTOR signaling system in the lipogenesis and differentiation of human meibomian gland epithelial cells (HMGECs). Treatment of HMGECs with rapamycin resulted in a reduction in lipid synthesis and the expression of PPARγ and SREBP-1, the major regulators of lipid synthesis. The phosphorylation of p70S6kinase and AKT, which are downstream signals of mTOR complexes 1 and 2, respectively, decreased following rapamycin treatment. In addition, when both mTOR complex 1 and 2 were suppressed using siRNA, there was a significant reduction in the expression of PPARγ and SREBP-1, along with a decrease in lipid synthesis in HMGECs. Our findings suggest that inhibiting the mTOR pathway diminishes the differentiation and adipogenesis of meibomian gland epithelial cells, and both mTOR complexes 1 and 2 appear to play a role in this activity.