Chronic AICAR‐induced AMP‐dependent kinase (AMPK) activation exerts an anti‐lipogenic effect in isolated rat adipocytes

In the present study, we investigated the effects of chronic AICAR‐induced AMP‐dependent kinase (AMPK) activation on lipid metabolism in isolated rat adipocytes. Isolated rat epididymal fat cells were incubated with AICAR (0.5mM) for 15h in vitro, or extracted from rats injected in vivo with AICAR for 14 days. We found that adipocytes exposed to AICAR elicited an ~80% reduction in FA uptake, which was accompanied by a ~3.5‐fold increase in FA oxidation. This indicates that FAs entering the adipocyte were being diverted towards the oxidative pathway. In accordance with these observations, we also found a reduction in acetyl‐CoA carboxylase (ACC) expression, which is a critical regulator of lipid synthesis and malonyl‐CoA content in the cell. We also observed that chronic AICAR exposure increased the lipolytic response under basal (~8‐fold) and epinephrine‐stimulated (~2‐fold) conditions as demonstrated by the release of free FAs in the medium. Here, we provide novel evidence that chronic AICAR‐induced AMPK activation reduces FA uptake, diverts metabolism of FAs towards oxidation, and promotes a lipolytic response. Altogether, these data indicate that chronic AMPK activation exerts an anti‐lipogenic effect in adipocytes, and may be a potential avenue for therapies targeted towards obesity and its related metabolic disorders. This research was funded by NSERC, CIHR, and CDA operating grants.