Adipose Tissue–Specific Knockout of AMPK alpha1/alpha2 Results in Normal AICAR Tolerance and Glucose Metabolism

AMP-activated protein kinase (AMPK) is a member of Ser/Thr kinases that has been shown to regulate energy balance. Although recent studies have demonstrated the function of AMPK in adipose tissue using different fat-specific AMPK knockout mouse models, the results were somewhat inconsistent. Our previous study has shown that exercise training increases AMPK activity in mouse adipose tissue, whereas high fat diet decreases its activity. For this study, we tested the hypothesis that AMPK in adipose tissue regulates whole body glucose metabolism. To determine the role of adipose tissue AMPK in vivo, we generated fat-specific AMPKα1/α2 knockout mice (AMPKFKO) using the Cre-loxP system. AMPK α1 and α2 protein expression in epididymal, inguinal, and brown adipose tissues was reduced by >90% in AMPKFKO mice compared to wild type littermates. Body weights of AMPKFKO mice were not different between 8-27 weeks of age. Furthermore, tissue weights (liver, kidney, muscle, heart and white and brown adipose tissue) were similar to wild type littermates and DEXA scan analysis revealed no differences in percentages of body fat and lean mass. Knockout of AMPKα1/α2 in adipose tissue abolished basal and AICAR-stimulated AMPK phosphorylation. Basal and AICAR-stimulated phosphorylation of Acetyl-CoA Carboxylase, a downstream of AMPK, was also reduced by 90% in AMPKFKO mice. Despite of the ablation of AICAR-stimulated AMPK phosphorylation, the blood glucose lowering effect of AICAR injection (i.p.) was normal in AMPKFKO mice. In addition, AMPKFKO displayed normal fasting blood glucose, glucose tolerance, and insulin tolerance, indicating normal whole body glucose metabolism. These data demonstrate that adipose tissue AMPK plays a minimum role in whole body glucose metabolism under normal condition. Disclosure R. Choi: None. A. McConahay: None. M.B. Johnson: None. H. Koh: None.