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. Author manuscript; available in PMC: 2014 Aug 22.
Published in final edited form as: Nature. 2013 Oct 24;502(7472):550–554. doi: 10.1038/nature12710

Extended Data Figure 4. Requirement of hepatic PPARδ and muscle PPARα for the inter-organ communication mediated by PC(18:0/18:1)/SOPC.

Extended Data Figure 4

a. Cd36 gene expression in muscle of wt and LPPARDKO mice under daytime restricted feeding (n=3, each time point). #p<0.05 (ANOVA). b. Effects of GW501516 on serum TG and muscle FA uptake in wt and LPPARDKO mice (n=5). c. Cd36 and Fabp3 gene expression in C2C12 myotubes treated with vehicle or 25 µM PC(18:0/18:1) (n=3). d. FA uptake in control or stable Cd36 knockdown C2C12 myotubes pretreated with indicated lipids. e. The mammalian one-hybrid assay (diagram shown on the top) to determine the trans-activation activity of the PPAR ligand binding domain (LBD) (n=3). Left panel: Relative luciferase unit (RLU, presented as fold change) indicative of the reporter activity regulated by Gal4 DNA binding domain (DBD)- PPARαLBD fusion protein (Gal4-PPARαLBD) in 293 cells treated with indicated phospholipids at 100 µM. Right panel: RLU of Gal4-PPARδLBD and Gal4-PPARγLBD treated with 100 µM PC(18:0/18:1). f. Heat map showing serum phospholipid changes between ZT20 and ZT8 in 7-month old male C57BL/6J mice on chow (n=3) or high fat diet (HFD for 4 months, n=5) from targeted metabolomics. g. Serum PC(36:1) concentrations under chow or HFD. h. Blood glucose levels of ad lib fed db/db mice measured between ZT0 and ZT3 before daily lipids injections [vehicle: n=4; PC(18:0/18:1): n=5]. i. Model for the role of PPARδ-PC(18:0/18:1)-PPARα signaling in FA synthesis and utilization in the liver-muscle axis. j. Upper panel: In vivo fatty acid uptake in soleus and gastrocnemius muscle 4 hours after vehicle or 5 mg/kg PC(16:0/18:1) injection though the tail vein (n=6); lower panel: muscle Cd36 and Fabp3 gene expression after PC(16:0/18:1) injection (n=4). k. Upper panel: activities of a PPRE-containing luciferase reporter in PPARα-expressing C2C12 cells treated with vehicle, 50 µM PC(18:0/18:1) or PC(16:0/18:1) and 1 µM GW7647 (a PPARα synthetic ligand). Lower panel: Cd36 expression in C2C12 myotubes. *p<0.05, (t-test), data presented as mean±SEM.