Extended Data Fig. 9: Sarcolipin abundance is regulated by TUG and is decreased in diet-induced insulin resistance.

a, WT and MTKO mice were housed at 30 °C from the time of weaning. At age 20 weeks, mice were fasted, treated with IP insulin-glucose or saline control, and sacrificed 3 h later. Hindlimb muscle lysates were immunoblotted as indicated. Data from replicates of this experiment were quantified and are plotted in Fig. 4b. b, WT and UBX mice were treated with IP insulin-glucose, or saline control, sacrificed after 30 min., and quadriceps muscles were immunoblotted as indicated. c,d, WT and MTKO mice were treated with IP insulin-glucose, or saline control, and sacrificed after 30 min. Hindlimb muscles were used for chromatin immunoprecipitation using PGC-1α (c) and PPARγ (d) antibodies, as indicated. PCR was used to detect an amplicon at -200 nucleotides relative to the sarcolipin transcription start site. e, WT mice were fed regular chow (RC) or a high-fat diet (HFD) for 3 weeks, then treated for 30 min. with IP insulin-glucose, or saline control. Quadriceps lysates were immunoblotted to detect intact TUG and the C-terminal cleavage product. Replicates were quantified using densitometry and are plotted in Fig. 4f. f, WT mice were fed RC or a HFD for 3 weeks, fasted, and sacrificed. Hindlimb muscles were isolated and immunoblotted as indicated. Replicates were quantified using densitometry and are plotted in Fig. 4g.