Chronic activation of AMP-activated protein kinase-alpha1 in liver leads to decreased adiposity in mice

被引：47

作者：

Yang, Jian ^{[1
]}

Maika, Shanna ^{[2
]}

Craddock, Lauren ^{[1
]}

King, Judy A. ^{[3
,4
,5
]}

Liu, Zhi-Mei ^{[1
]}

机构：

[1] Univ S Alabama, Coll Med, Dept Physiol, Mobile, AL 36688 USA

[2] Univ Texas Austin, Inst Mol & Cellular Biol, Austin, TX 78712 USA

[3] Univ S Alabama, Coll Med, Dept Pharmacol, Mobile, AL 36688 USA

[4] Univ S Alabama, Coll Med, Dept Pathol, Mobile, AL 36688 USA

[5] Univ S Alabama, Coll Med, Ctr Lung Biol, Mobile, AL 36688 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 370卷 / 02期

关键词：

AMPK-alpha1; transgenic mice; SREBP; liver gene expression;

D O I：

10.1016/j.bbrc.2008.03.094

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To assess the metabolic effects of chronic activation of AMP-activated protein kinase (AMPK) in liver, we generated a new transgenic (Tg) mouse model expressing constitutively active (CA)-AMPK-alpha1 in liver. In the short-term activation, the TgCA-AMPK-alpha 1 mice exhibited minimal phenotype, but the Tg liver had elevated sterol regulatory element-binding protein (SREBP)-2 mRNA level and a parallel increase in transcripts of its target genes. UCP2 mRNA level was elevated. In the long-term activation, the TgCA-AMPK-alpha 1 mice had markedly reduced white fat mass. The Tg liver had reduced mRNA expression of SREBP-1c and its target genes. Remarkably, the Tg mice were resistant to a high-fat diet-induced obesity. These data suggest that short-term chronic activation of AMPK-alpha 1 in liver leads to compensatory increase in lipogenic gene expression due to increased SREBP-2 expression, and long-term chronic activation of AMPK-alpha 1 decreases expression of SREBP-1c and its target genes, which results in reduced fat storage. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：248 / 253

页数：6

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