AMP激活的蛋白激酶抑制肝G2细胞中LXR/SREBP-1信号诱导的ANGPTL8的表达。
AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells.
作者信息
Lee Jinmi, Hong Seok-Woo, Park Se Eun, Rhee Eun-Jung, Park Cheol-Young, Oh Ki-Won, Park Sung-Woo, Lee Won-Young
机构信息
Institute of Medical Research, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 110-746, South Korea.
出版信息
Mol Cell Endocrinol. 2015 Oct 15;414:148-55. doi: 10.1016/j.mce.2015.07.031. Epub 2015 Aug 4.
ANGPTL8 is a liver-derived secretory protein that leads to elevated serum triglyceride and the level of circulating ANGPTL8 is strongly associated with obesity and diabetes. Here we investigated the mechanisms of activation and inhibition of ANGPTL8 expression in hepatocytes. The expression of ANGPTL8 was significantly increased in HepG2 cells exposed to palmitic acid, tunicamycin, or T0901317, and was reversed in cells treated with AICAR. Palmitic acid, tunicamycin, and T0901317 increased LXRα and SREBP-1c mRNA expression. The inhibitory effect of AICAR on the expression of T0901317-induced ANGPTL8 was most strongly evident in cells that were transfected with SREBP-1 siRNA. AICAR increased phosphorylation of PPARα and the effect of AICAR was not observed in cells treated with PPARα inhibitor. Metformin had a similar effect on ANGPTL8 expression to that of AICAR. These data suggest that AMPK can suppress the expression of LXR/SREBP-1 signal-induced ANGPTL8 in HepG2 cells.
血管生成素样蛋白8（ANGPTL8）是一种肝脏来源的分泌蛋白，可导致血清甘油三酯升高，且循环中ANGPTL8的水平与肥胖和糖尿病密切相关。在此，我们研究了肝细胞中ANGPTL8表达的激活和抑制机制。在暴露于棕榈酸、衣霉素或T0901317的HepG2细胞中，ANGPTL8的表达显著增加，而在用AICAR处理的细胞中则逆转。棕榈酸、衣霉素和T0901317增加了肝X受体α（LXRα）和固醇调节元件结合蛋白-1c（SREBP-1c）的mRNA表达。AICAR对T0901317诱导的ANGPTL8表达的抑制作用在转染了SREBP-1小干扰RNA（siRNA）的细胞中最为明显。AICAR增加了过氧化物酶体增殖物激活受体α（PPARα）的磷酸化，在用PPARα抑制剂处理的细胞中未观察到AICAR的作用。二甲双胍对ANGPTL8表达的影响与AICAR相似。这些数据表明，腺苷酸活化蛋白激酶（AMPK）可以抑制HepG2细胞中LXR/SREBP-1信号诱导的ANGPTL8表达。
Zotero 插件