Figure 2.

KL and its KL1 subdomain alter the hippocampal metabolome. A, Diagram of the full-length klotho protein (top, amino acids 1–1014) including its subdomains and (bottom, amino acids 58–506) the KL1 protein. B, Experimental paradigm for performing targeted metabolomic analysis of mice that were treated with vehicle (Veh), human KL (10 μg/kg, s.c.), or human KL1 (10 μg/kg, s.c.). Male mice (age, 4 months; n = 12–13/experimental group) were treated. Four hours later, hippocampi were collected, flash frozen, and then underwent targeted metabolomic profiling. C, PCA plot of normalized counts of metabolites extracted from hippocampus shows clear separation among the three treatment groups on components 2 and 3. D, Volcano plot showing the significantly differentially expressed metabolites in the KL- compared with Veh- treated group. E, Volcano plot showing the significantly differentially expressed metabolites in the KL1- compared with the Veh-treated group. In D and E, the 15 labeled metabolites are all shared between KL- and KL1-treated groups. PC, principal component.