Figure a Legends
Figure 1. Schematic diagram of experiment study design showing mice groups, chronogram, dietary and treatment intervention.
Figure 2. Effects of agomelatine (10, 25 and 50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) administration on (A) body weight evolution; (B) energy intake and energy efficiency, and; (C) epididymal and abdominal fat in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 3. Result of the administration of agomelatine (10, 25 and 50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) on (A) glucose tolerance test and area under the curve (AUC); (B) basal glucose, insulin levels, and HOMA-IR index; and (C) Total, LDL- and HDL- Cholesterol plasma levels in high fat diet (HFD) group. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 4. Impact of agomelatine (10, 25 and 50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) administration on inflammatory status. (A) Fat and liver gene expression of Tnf-α ,Il-1β , Il-6 and Mcp-1 ; (B) Liver gene expression ofJnk-1 ; (C) fat gene expression of Leptin , Leptin receptor , and Adiponectin and liver expression ofLeptin receptor; (D) fat and liver gene expression ofGlut-4 and Ampk in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 5. Effects of agomelatine (10, 25 and 50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) administration on hepatic Total, Ly6C+CD11b+ and CD45+CD11bint immune-cell populations, and total and CD45+CD11bint immune-cell populations in adipose tissue in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 6. Influence of agomelatine (10, 25 and 50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) administration on (A) colonic gene expression of Muc-2 , Muc-3 , Occludin ,Tff-3 and Zo-1 , and; (B) hepatic gene expression ofTlr-4 in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 7. Impact of the administration of agomelatine (50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) on (A) microbiota diversity (Chao1, Shannon index and Observed OTUs); (B) beta-diversity by principal coordinate analysis score plot, and; (C) bacterial phyla and F/B ratio in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 8. Effect of agomelatine (50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) administration on microbiota diversity at the order level in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 9. (A) Metagenomic functional features predicted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) that were differentially abundant and drove differences in control, untreated and agomelatine, melatonin or metformin treated HFD-fed mice. Effect of the administration of agomelatine (50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) on the (B) Relative abundance of short fatty acid (SCFA)-producing bacteria, and on the (C) Acetate:Propionate ratio in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).
Figure 10. Effect of agomelatine (10, 25 and 50 mg/kg), melatonin (15 mg/kg) and metformin (250 mg/kg) administration on (A) aortic endothelial function, and; (B) aortic NADPH activity in high fat diet (HFD)-fed mice. Data are expressed as means ± SEM (n=8). Groups with different letters statistically differ (p< 0.05 ).