Fig. 7: GLP-1RA/tesaglitazar effects on the hypothalamic proteome and cFOS.
From: GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice
a,b, Representative immunofluorescence (a) and quantification (b) of cFos positive neurons in the ARC of 47-week-old male DIO mice after single s.c. treatment with Vhcl or 150 nmol kg−1 of GLP-1RA, tesaglitazar or GLP-1RA/tesaglitazar (n = 4/4/4/3 mice; scale bar, 100 µm). c–h, LC–MS analysis of acute drug effects on the hypothalamic proteome. c, Identified total number of quantified protein groups across all samples, as well as significantly changed number of proteins as determined by ANOVA (FDR < 0.025). d,e, PCA of proteomic samples (d) and heat map of z-scored protein intensities among all significantly changed proteins (e). f, List of proteins upregulated by tesaglitazar and by GLP-1/tesaglitazar. g,h, Selected gene annotations positively enriched in the specific treatment groups (g) and heat map of kinases significantly changed (ANOVA, FDR < 0.025) by the respective treatment groups (h). Proteins are grouped by hierarchical clustering, colouring represents z-scored protein intensities. Data in a and b were obtained after 90 min of drug exposure in n = 4/4/4/3 mice, data in c–h were obtained after 10 h of drug exposure in 49-week-old C57BL6J DIO mice (n = 5 mice each group). Data in b were analysed by one-way ANOVA and Fisher’s least-significant difference test. Data represent means ± s.e.m.; asterisks indicate *P < 0.05, **P < 0.01. Exact P values for treatment effects are: b P = 0.0138 (Vhcl versus tesaglitazar), P = 0.0466 (Vhcl versus GLP-1RA/tesaglitazar), P = 0.0326 (GLP-1RA/tesaglitazar versus tesaglitazar) and P = 0.0093 (GLP-1RA versus tesaglitazar).
