膳食饱和脂肪通过PGC-1β对SREBP的共激活作用产生的高脂血症效应。
Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP.
作者信息
Lin Jiandie, Yang Ruojing, Tarr Paul T, Wu Pei-Hsuan, Handschin Christoph, Li Siming, Yang Wenli, Pei Liming, Uldry Marc, Tontonoz Peter, Newgard Christopher B, Spiegelman Bruce M
机构信息
Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cell. 2005 Jan 28;120(2):261-73. doi: 10.1016/j.cell.2004.11.043.
The PGC-1 family of coactivators stimulates the activity of certain transcription factors and nuclear receptors. Transcription factors in the sterol responsive element binding protein (SREBP) family are key regulators of the lipogenic genes in the liver. We show here that high-fat feeding, which induces hyperlipidemia and atherogenesis, stimulates the expression of both PGC-1beta and SREBP1c and 1a in liver. PGC-1beta coactivates the SREBP transcription factor family and stimulates lipogenic gene expression. Further, PGC-1beta is required for SREBP-mediated lipogenic gene expression. However, unlike SREBP itself, PGC-1beta reduces fat accumulation in the liver while greatly increasing circulating triglycerides and cholesterol in VLDL particles. The stimulation of lipoprotein transport upon PGC-1beta expression is likely due to the simultaneous coactivation of the liver X receptor, LXRalpha, a nuclear hormone receptor with known roles in hepatic lipid transport. These data suggest a mechanism through which dietary saturated fats can stimulate hyperlipidemia and atherogenesis.
辅激活因子PGC-1家族可刺激某些转录因子和核受体的活性。固醇调节元件结合蛋白（SREBP）家族中的转录因子是肝脏中脂肪生成基因的关键调节因子。我们在此表明，导致高脂血症和动脉粥样硬化形成的高脂喂养会刺激肝脏中PGC-1β以及SREBP1c和1a的表达。PGC-1β与SREBP转录因子家族协同激活，并刺激脂肪生成基因的表达。此外，SREBP介导的脂肪生成基因表达需要PGC-1β。然而，与SREBP本身不同，PGC-1β可减少肝脏中的脂肪积累，同时大幅增加极低密度脂蛋白（VLDL）颗粒中的循环甘油三酯和胆固醇。PGC-1β表达后对脂蛋白转运的刺激可能是由于同时协同激活了肝脏X受体LXRα，这是一种在肝脏脂质转运中具有已知作用的核激素受体。这些数据提示了一种机制，通过该机制饮食中的饱和脂肪可刺激高脂血症和动脉粥样硬化形成。
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