Fasting induced up-regulation of activating transcription factor 5 in mouse liver

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• 作者：Yusuke I. Shimizu ; Momoko Morita ; Asako Ohmi ; Shun Aoyagi ; Hitomi Ebihara ; Daijuro Tonaki ; Yoko Horino ; Mika Iijima ; Hidenori Hirose ; Shigeru Takahashi ; Yuji Takahashi
• 关键词：Fasting ; Gluconeogenesis ; Stress response ; Nup62 ; Il4i1
• 刊名：Life Sciences
• 出版年：2009
• 出版时间：19 June 2009
• 年：2009
• 卷：84
• 期：25-26
• 页码：894-902
• 全文大小：819 K

文摘

Aims

Food deprivation (fasting) is commonly encountered in the lives of animals and humans. In mammals, adaptive responses predominantly include the induction of hepatic gluconeogenesis, but the regulatory mechanisms remain unclear. Atf5 (activating transcription factor 5) is a transcription factor of the ATF/cAMP response element-binding protein family and is expressed abundantly in human liver. Atf5 has been associated with stress responses, cell differentiation, proliferation, and survival. However, its role in the liver response to in vivo food deprivation has not yet been investigated.

Main methods

Adult mice were food-deprived for 48 h and the expression of two Atf5 mRNA subtypes (Atf5-R1 and Atf-R2) and gluconeogenic factors was investigated. Using in vitro cell culture, Pgc-1α (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) promoter activities after ectopic expression of Atf5 and Cebpg (CCAAT/enhancer-binding protein gamma) proteins were measured.

Key findings

The Atf5-R1 transcript was found to be abundant in liver and other energy metabolism-related organs; Atf5-R2 was prominent in the testis. Fasting resulted in elevation of the expression of both Atf5-R1 and R2 in the liver. Interestingly, up-regulation of Atf5 was accompanied by increased expression of Cebpg and Pgc-1α. In human hepatoma cells (HepG2), but not in human cervical carcinoma cells (HeLa), forced expression of Atf5 and Cebpg cooperatively stimulated Pgc-1α promoter activity, suggesting that hepatic Pgc-1α could be induced by Atf5 and Cebpg in cooperation with other hepatic factors.

Significance

Hepatic Atf5 might be potentially involved in the induction of gluconeogenetic factors during in vivo fasting stress.