Metabolism Section, Department of Veterans Affairs Medical Center, University of California-San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
Innate Immun. 2011 Apr;17(2):174-82. doi: 10.1177/1753425909357578. Epub 2010 Jan 25.
Carbohydrate response element binding protein (ChREBP) is a recently discovered transcription factor whose levels and activity are increased by glucose leading to the activation of target genes, which include acetyl-CoA carboxylase, fatty acid synthase, and liver-type pyruvate kinase. Here, we demonstrate that lipopolysaccharide (LPS) treatment causes a marked decrease in ChREBP mRNA and protein levels in the liver of mice fed a normal chow diet or in mice fasted for 24 h and then re-fed a high carbohydrate diet. This decrease occurs rapidly and is a sensitive response (half-maximal dose 0.1 μg/mouse). The decrease in ChREBP is accompanied by a decrease in the expression of ChREBP target genes. Zymosan and turpentine treatment also decrease hepatic ChREBP levels and the expression of its target genes. Additionally, tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) decrease liver ChREBP expression both in vivo and in Hep3B cells in culture. Finally, LPS decreased ChREBP expression in muscle and adipose tissue. These studies demonstrate that ChREBP is down-regulated during the acute phase response resulting in alterations in the expression of ChREBP regulated target genes. Thus, ChREBP joins a growing list of transcription factors that are regulated during the acute phase response.
碳水化合物反应元件结合蛋白（ChREBP）是一种新发现的转录因子，其水平和活性可被葡萄糖升高所激活，进而激活包括乙酰辅酶 A 羧化酶、脂肪酸合成酶和肝型丙酮酸激酶在内的靶基因。在这里，我们证明了脂多糖（LPS）处理会导致正常饮食喂养的小鼠或禁食 24 小时后再喂食高碳水化合物饮食的小鼠肝脏中的 ChREBP mRNA 和蛋白水平显著降低。这种降低发生得很快，是一种敏感的反应（半最大剂量为 0.1μg/只）。ChREBP 的降低伴随着 ChREBP 靶基因表达的降低。酵母聚糖和松节油处理也会降低肝 ChREBP 水平及其靶基因的表达。此外，肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）在体内和培养的 Hep3B 细胞中均降低肝脏 ChREBP 的表达。最后，LPS 降低了肌肉和脂肪组织中的 ChREBP 表达。这些研究表明，ChREBP 在急性期反应过程中被下调，导致 ChREBP 调节的靶基因表达发生改变。因此，ChREBP 加入了在急性期反应过程中被调节的越来越多的转录因子之列。
