Figure 3.

Comparison of metabolite changes associated with leptin replacement with those associated with acute caloric restriction (A-B.) Comparison at the level of metabolite sets based on the metabolite-set enrichment analysis of sub-pathways in Fig. 1B. In each plot, the top row illustrates fold-changes in metabolites in patients with congenital leptin deficiency post- vs pre-leptin treatment and the bottom row illustrates fold-changes upon caloric restriction versus baseline (data obtained from (15); dark columns indicate metabolites with a reported statistically significant change after caloric restriction, FDR q value < 0.05). Metabolites are sorted by increasing fold-change. Metabolite sub-pathways which tend towards an increase (A) or decrease (B) upon leptin treatment are shown (also seeFig. 1B; Table S2 (21)). (C-E.) Comparison at the level of individual metabolites. The scatterplots of individual metabolites show fold-change in “caloric restriction versus baseline” (as reported in (15); y-axis) versus acute fold-change upon leptin replacement therapy (x-axis). (C) shows the sub-pathways which have a consistent direction in the 2 studies. (D-E) show the sub-pathways with opposing or inconsistent directions of change between the 2 studies.