Leptin Silencing Attenuates Lipid Accumulation through Sterol Regulatory Element-Binding Protein 1 Inhibition in Nasopharyngeal Carcinoma

Sheng Dean Luo, Hsin Ting Tsai, Tai Jan Chiu, Shau Hsuan Li, Ya Ling Hsu, Li Jen Su, Meng Hsiu Tsai, Ching Yi Lee, Chang Chun Hsiao, Chang Han Chen

研究成果: 雜誌貢獻期刊論文同行評審

摘要

Leptin is a crucial regulator of metabolism and energy homeostasis in mammals. Many studies have investigated the impacts of leptin on human cancers, such as proliferation and metastasis. However, the mechanisms underlying leptin-mediated regulation of lipid metabolism in nasopharyngeal carcinoma (NPC) remain incompletely understood. In the current study, leptin downregulation ameliorated lipid accumulation, triglyceride, and cholesterol levels. Mechanistically, diminished leptin by siRNA not only inhibited sterol regulatory element-binding protein 1 (SREBP1), a master regulator of lipid metabolism, at the mRNA and protein levels, but also reduced SREBP1 downstream target expressions, such as fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1), in NPC cells. In addition, leptin expression could modulate the promoter activity of SREBP1. We also found that pharmacological inhibition of poly-ADP ribose polymerase-γ (PPAR-γ) resulted in increased SREBP1 expression in leptin-depleted NPC cells. Functionally, SREBP1 overexpression overcame the effects of leptin-silencing attenuated triglyceride level, cholesterol level and cell survival in NPC cells. Taken together, our results demonstrate that leptin is an important regulator of lipid metabolism in NPC cells and might could be a potential therapeutic target for treatment of NPC patients.

原文???core.languages.en_GB???
文章編號5700
期刊International Journal of Molecular Sciences
23
發行號10
DOIs
出版狀態已出版 - 1 5月 2022

指紋

深入研究「Leptin Silencing Attenuates Lipid Accumulation through Sterol Regulatory Element-Binding Protein 1 Inhibition in Nasopharyngeal Carcinoma」主題。共同形成了獨特的指紋。

引用此