Akt signaling mediates the anabolic action of sympathetic innervation in brown adipose tissue from cold‐exposed rats (1161.6)

Abstract

Previous studies from our lab have demonstrated that sympathetic nervous system (SNS) exerts an anabolic effect on muscle protein metabolism. However, the physiological role of SNS in the maintenance of brown adipose tissue (BAT) mass, the main site of organism heat production, is unclear. Thus, our goal was to investigate the adrenergic mechanisms controlling BAT protein metabolism. For this, adult Wistar rats were submitted to surgical sympathetic hemidenervation (DEN) of BAT. Six days later, rats were exposed to cold (4oC) for 2 days. The phosphorylation levels of proteins involved in the control of proteolytic pathways and protein synthesis were analyzed by Western blotting. BAT noradrenaline was measured by HPLC. Cold‐exposed animals exhibited an increase in BAT noradrenaline content and in the levels of total (2‐fold) and mitochondrial (60%) proteins. These effects were associated with an up‐regulation in the phosphorylation levels of AktSer (70%), GSK3α (30%) and 4E‐BP1 (2‐fold), which are key mediators involved in protein synthesis. Furthermore, BAT from cold‐exposed animals also showed an increase in the phosphorylation levels of the transcription factor Foxo1, which could inhibit the expression of proteolytic genes. All these effects were abolished in cold‐exposed rats submitted to DEN. In summary, the data suggest that SNS plays an important role in cold‐induced increase in total and mitochondrial proteins in BAT and these effects may be partially mediated by downstream targets of AKT such as FoxO1, GSK3a and 4E‐BP1.Grant Funding Source: Supported by CNPq and FAPESP (13/17111‐0; 12/24524‐6).