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Chronic Activation of AMP‐Activated Protein Kinase (AMPK)‐alpha1 in Liver Leads to Decreased Adiposity in Mice Fed A Normal or High‐Fat Diet
Author(s) -
Yang Jian,
Maika Shanna,
King Judy A.,
Liu ZhiMei
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a454-d
Subject(s) - medicine , endocrinology , ampk , adipose tissue , amp activated protein kinase , protein kinase a , fatty liver , chemistry , steatosis , white adipose tissue , biology , kinase , biochemistry , disease
The AMP‐activated protein kinase (AMPK) is a heterotrimeric complex comprising alpha, beta and gamma subunits. Short‐term overexpression of constitutively active (CA)‐AMPK‐alpha2 in liver reportedly leads to hypoglycemia and fatty liver. However, the consequences of chronic activation of AMPK in liver have not yet been determined. Here, we describe a new transgenic (Tg) mouse model expressing CA‐AMPK‐alpha1 in liver. The CA‐AMPK‐alpha1 mice fed a normal diet had markedly reduced white adipose tissue mass and hepatic glycogen content with little change in hepatic triglyceride content and plasma levels of free fatty acids and triglycerides in fed state, but hepatic cholesterol content remained higher than wild‐type control. Surprisingly, the Tg liver had elevated SREBP‐2 mRNA level and a parallel increase in transcripts of SREBP‐2 target genes (e.g., ACC , FAS , and HMG CoA reductase ). Despite the elevated hepatic malonyl CoA content, fatty acids continued to be oxidized as indicated by unchanged plasma 3‐hydroxybutyrate level. Remarkably, the Tg mice were resistant to a high‐fat diet‐induced obesity. These data suggest that despite causing a compensatory increase in lipid synthesis chronic activation of AMPK in liver leads to persistent oxidation of fatty acids, which results in increased energy dissipation in liver and thus reduced fat storage in adipose tissue. Supported by AHA Grant #0635341N.