Fig. 1.

CHP prevents weight gain and fat accumulation and improves plasma biomarkers in the NAFLD mouse model.

(A) Our NAFLD model was established through a combination of WD and thermoneutrality housing. Mice were housed in a thermoneutrality cabinet from 6 weeks of age. A specific diet (CD/WD) was introduced at Week 7. Treatment with CHP (20 mg/kg) was started at Week 7 and was given by gavage 3 times per week, for the whole duration of the study. Evaluation of fat mass by EchoMRI™ was performed at Week 18. Fasting glycaemia was measured at Week 20. Mice were euthanised at Week 24, after a 3-h fast. (B) Body weight increase over time. Weight was recorded once a week. (C) Body weight at Week 24. (D) Body fat percentage measured at Week 18 by MRI. (E–G) LDL-cholesterol (E), ALT (F), and CRP (G) levels in plasma. Blood was collected at the end of the experiment. (H) Glycaemia as measured after an overnight (14 h) fast. (I) HOMA-IR index for each group, calculated following the homeostatic model assessment (n = 6–8). Results represent the mean ± standard deviation (B) and the whiskers in boxplots represent the minimum to maximum range (C–I). Two-way ANOVA (B) and one-way ANOVA (C–I), followed by Dunnett’s multiple comparison test vs. WD group, were used for statistical analysis. ∗p <0.05; ∗∗p <0.01; ∗∗∗p <0.001; ∗∗∗∗p <0.0001. ALT, alanine transaminase; ANOVA, analysis of variance; CD, chow diet; CHP, cyclo(His-Pro); CRP, C-reactive peptide; HOMA-IR, homeostatic model assessment-insulin resistance; LDL, low-density lipoprotein; MRI, magnetic resonance imaging; NAFLD, non-alcoholic fatty liver disease; TN, thermoneutral housing; WD, western diet.