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AMPK regulation of cardiac growth‐related signaling in ob/ob mice following 2 weeks of AICAR treatment
Author(s) -
Williamson David L,
Alway Stephen E
Publication year - 2008
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.22.1_supplement.751.6
Subject(s) - ampk , medicine , endocrinology , phosphorylation , p70 s6 kinase 1 , protein kinase a , activator (genetics) , muscle hypertrophy , chemistry , biology , protein kinase b , receptor , microbiology and biotechnology
The aim of this study was to determine how AMP‐activated protein kinase (AMPK) regulates cardiac growth‐related pathways in lean and obese mice. 12 wk old male ob/ob (body weight (BW)=57.9g) and lean wild type (BW=30.3g) mice received and injection of 0.5 mg/g BW AICAR (AIC) in saline or a vehicle control (CON) for 2 wks. All mice were sacrificed 24 hrs after the last injection, including a 12 hr fast. Heart weights did not change for any of the groups. Western analysis of heart lysate from fasted ob/ob CON mice displayed reduced AMPK T172 and ACC S79 phosphorylation compared with lean CON, which increased in both groups after the 2 wk AIC treatment. Immunoprecipitations (IP) of tuberin displayed a reduced association with hamartin in ob/ob CON versus the lean CON, which relatively increased in both groups following AIC treatment. IPs for mTOR displayed comparable levels of raptor association in the CON groups, and increased similarly following AIC treatment. Fasted ob/ob CON mice displayed higher S6K1 T389, ribosomal protein S6 S240/244, and 4E‐BP1 T37/46 phosphorylation than lean CON, which was attenuated by AIC treatment. These data suggest that obese mice display elevated cardiac growth‐related signaling that precedes cardiac hypertrophy, and acute treatment with an AMPK activator attenuates growth‐signaling and the progression toward cardiac hypertrophy. Support: WVU Research Development Grant NT10023W (to DLW)