Experimental protocol

Male Floxed and IL‐6 MKO mice were at the age of 8 weeks divided in three groups. A group receiving standard rodent chow (Altromin 1314F, Brogaarden, Lynge, Denmark) (Chow), a group receiving a high‐fat diet (HFD) with 60% of calories from fat (Altromin C1090‐60, Brogaarden, Lynge, Denmark), and a group receiving HFD in combination with having access to a running wheel (diameter 24.2 cm, Mini‐mitter) (HFD ExTr) for 16 weeks (n = 10). The running wheels were blocked occasionally ensuring that the two exercise training groups were running a similar distance (~ 20 km/week, with an average pace of 26.0 ± 1.6 m/min for Floxed and 23.7 ± 0.4 m/min for IL‐6 MKO). Additionally, to increase the exercise load and increase adaptation to exercise, HFD ExTr mice were during the last 4 weeks running on a treadmill (303401 series, TSE systems, Germany) 60 min 3 days a week at 13.8 m/min and 10° incline the first week increasing to 16.2 m/min and 10° incline the last week. At the end of the experimental period, the running wheels were blocked 24 h before euthanization. Ad libitum access to food and water was maintained. The mice were euthanized by cervical dislocation and livers were removed and snap frozen in liquid nitrogen. Trunk blood was collected and centrifuged at 2600 g, 4°C for 15 min to generate plasma. All samples were then stored at −80°C.