Fig. 2: Chronic high-dose effects of GLP-1RA/tesaglitazar in obese and lean mice.
From: GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice
a–d, Effects on body weight (a), cumulative food intake (b) and change of fat (c) and lean tissue mass (d) in 34-week-old male C57BL/6J DIO mice treated for 14 days with 50 nmol kg−1 per day. e,f, Fasting levels of blood glucose (e) and insulin (f) at study day 7. g,h, i.p. insulin tolerance (ipITT) assessed at day 14: blood glucose (g) and AUC (h). i, In vivo glucose-stimulated insulin secretion (GSIS) in 47-week-old male DIO mice treated i.p. with 1.5 g glucose per kg body weight (blood was collected at time points 0 and 15 min after glucose injection) (i). j–m, Expression of Fabp4 (j) and Plin2 (k) in liver and of Arntl (l) and Sema3c (m) in skeletal muscle of 30-week-old male DIO mice treated for 3 days with 50 nmol kg−1 per day. n–s, Changes in body weight (n), plasma levels of cholesterol (o), triglycerides (p), aspartate-aminotransferase (q), alanine-transferase (r) as well as heart weight (s) in 16-week-old male lean C57BL/6J mice after 14 days treatment with 50 nmol kg−1 per day. t, Plasma levels of creatinine in 44-week-old male C57BL/6J DIO mice treated for 14 days with vehicle (Vhcl) or GLP-1RA/tesaglitazar at a dose of 10, 25 or 50 nmol kg−1 per day (n = 8 mice each group). Sample sizes for treatment with Vhcl, GLP-1RA, tesaglitazar or GLP-1RA/tesaglitazar (a–m) are n = 8/8/8/8 mice (a,d,f,j,k), n = 8/7/8/8 mice (c,i,m), n = 7/8/8/8 mice (e) and n = 8/8/8/7 mice (g,h,l). Cumulative food intake (b) was assessed per cage in n = 4/4/4/4 cages containing n = 8/8/8/8 mice. Sample sizes for treatment with Vhcl, tesaglitazar, GLP-1RA + tesaglitazar or GLP-1RA/tesaglitazar (n–s) are n = 8/7/8/7 mice (n), n = 8/8/8/7 mice (o–q,s) and n = 8/8/7/7 mice (r). Data represent means ± s.e.m. Data in a, b, g and n have been analysed by two-way ANOVA with Bonferroni post hoc comparison for individual time points. Data in c–f, h–m and o–t have been analysed by one-way ANOVA using the Bonferroni’s multiple comparison test. Asterisks indicate *P < 0.05, **P < 0.01, ***P < 0.001. Exact P values for treatment effects are a all P ≤ 0.0001; b P = 0.043; c all P < 0.0001, d P = 0.0007 (versus Vhcl) and P = 0.0010 (versus GLP-1RA); e P = 0.0106; f P = 0.0216 and P = 0.0035; g P = 0.0064; h P = 0.0011 and P = 0.0359; i P = 0.024 (Vhcl versus GLP-1RA), P = 0.0143 (Vhcl versus GLP-1RA/tesaglitazar), P = 0.0125 (GLP-1RA versus GLP-1RA/tesaglitazar), P = 0.0072 (tesaglitazar versus GLP-1RA/tesaglitazar; j all P < 0.0001; k all P < 0.0001; l P = 0.0127; m P = 0.0032; n P = 0.0002 (GLP-1RA + tesaglitazar versus Vhcl), all other P < 0.0001; o P = 0.0012 (GLP-1RA + tesaglitazar versus Vhcl), P = 0.0008 (GLP-1RA/tesaglitazar versus tesaglitazar), P = 0.0020 (Vhcl versus tesaglitazar); p P = 0.0031. For exact P values at individual time points (a,b,g,n), see the data source file.
