Chronic activation of AMP-activated protein kinase-alpha1 in liver leads to decreased adiposity in mice - PubMed (original) (raw)

. 2008 May 30;370(2):248-53.

doi: 10.1016/j.bbrc.2008.03.094. Epub 2008 Mar 31.

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

Jian Yang et al. Biochem Biophys Res Commun. 2008.

Abstract

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-alpha1 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-alpha1 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-alpha1 in liver leads to compensatory increase in lipogenic gene expression due to increased SREBP-2 expression, and long-term chronic activation of AMPK-alpha1 decreases expression of SREBP-1c and its target genes, which results in reduced fat storage.

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