Figure 1.

Schematic overview of the experimental setup. Rats were maintained on standard chow (SC; n = 10) or cafeteria diet (CAF; n = 20) for 13 weeks (W). The CAF diet was comprised of a free choice between SC and a high fat/sweet diet, both provided at libitum, and intermittent additional access to human snacks. During these 13 weeks body weight (BW) was measured weekly and blood glucose (BG) and plasma lipid (PL) concentrations were assessed in week 11 and 13, respectively. Chronic vehicle (Veh) or ACT-335827 treatment (ACT; 300 mg/kg, p.o., once daily before onset of the dark phase) started in week 14. All SC fed rats received vehicle treatment only (SC-Veh; n = 10). The CAF diet fed rats were divided into a vehicle (CAF-Veh; n = 11) and an ACT-335827 (CAF-ACT; n = 9) treatment group based on an even distribution of their blood glucose and plasma triglyceride levels, measured in week 11 and 13. During weeks 14–17 the food and water intake and the body weight gain was assessed, and the feed conversion efficiency calculated. In week 16 cognitive hippocampal function was assessed using a contextual fear paradigm. In week 17 blood pressure (BP) measurements and an oral glucose tolerance test (oGTT) were performed. In the beginning of week 18 all rats were sacrificed. Their plasma lipid (PL) and plasma leptin levels were assessed and the weight of white adipose tissue deposits (WATs) and the interscapular brown adipose tissue (iBAT) deposit was measured. See the Methods for further details.