Figure 1.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on hepatic steatosis in high fat diet-induced obese mice.
(A) Representative pictures and histochemistry of the liver. Upper panel, pictures of the liver (bar length = 1 cm); middle panel, results of H&E staining; lower panel, results of Oil-red O staining. (B) Effect of combined treatment on triglyceride levels in the liver. (C) Effect of combined treatment increased liver weight. Values presented in (C) – (D) are average ± SD (n = 5); **p<0.01 vs control; #p<0.05 vs T0901317-treated animals.
Figure 2.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on blood levels of insulin, glucose, triacylglyceride, cholesterol, and free fatty acid.
(A) Blood glucose level. (B) Blood insulin level. (C) Results of HOMA-IR. (D) Blood triglyceride level. (E) Blood cholesterol level. (F) Blood free fatty acids level. Values represent average ± SD (n = 5); **p<0.01 vs control; #p<0.05 vs T0901317-treated animals; ##p<0.01 vs T0901317-treated animals.
Figure 3.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on glucose tolerance and insulin sensitivity.
(A) Glucose profiles of IPGTT. (B) Area under the curve (AUC) of IPGTT. (C) Results of ITT. Values represent average ± SD (n = 5); *p<0.05 vs control; **p<0.01 vs control; #p<0.05 vs T0901317-treated animals.
Figure 4.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on gene expression.
(A) – (E) The mRNA level of the genes involved in lipogenesis (srebp-1c, chrebp, acc1, fas, and scd1). (F) – (G) The mRNA level of genes involved in fatty acid transport and β-oxidation (cd36, cpt-1a). (H) - (I) The mRNA level of genes involved in gluconeogenesis (pepck and g6p). Values represent average ± SD (n = 4–5); **p<0.01 vs control; ##p<0.01 vs T0901317-treated animals.
Figure 5.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on fgf21 gene expression in liver and adipose tissue.
(A) The mRNA level of fgf21 in the liver. (B) The mRNA level of fgf21 in adipose tissue. Values represent average ± SD (n = 4); **p<0.01 vs control; ##p<0.01 vs T0901317-treated animals.
Figure 6.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on adipocyte size.
(A) Images of adipose tissue (bar length = 1 cm) and sections of adipose tissue. (B) Percentage of cells with defined range of diameters. (C) Average size of adipocytes. **p<0.01 vs control; #p<0.05 vs T0901317-treated animals.
Figure 7.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on glycerol release from WAT.
(A) Time course of the glycerol release. (B) AUC of the glycerol release. Values represent average ± SD (n = 3); **p<0.01 vs control.
Figure 8.
Effect of T0901317 (T09), finofibrate (FF) or in combination (T09+ FF) on mRNA levels of selected genes in the adipose tissue.
(A) – (B) The mRNA levels of genes involved in cholesterol reverse transport (abca1 and abcg1). (C) The mRNA level of glut4 gene. (D) The mRNA level of plin1 gene. (E) – (F) The mRNA level of hsl and atgl genes. **p<0.01 vs control.
Figure 9.
The mRNA level of selected genes in adipose tissue.
(A) The mRNA level of leptin and adiponectin genes. (B) The mRNA level of lxrα, pparα, pparγ and pparδ. (C) The mRNA level of f4/80, cd11c and cd206. (D) The mRNA level of mcp1, tnfα, ifnγ and il1β Values represent average ± SD (n = 4); **p<0.01 vs control.
Figure 10.
Depicted pathway for the exacerbated hepatic steatosis caused by combined treatment.
Combined treatment activates LXR and PPARα, thereby increasing lipogenesis in the liver via elevating the transcription of srebp-1c, chrebp, acc1, fas and scd1. Meanwhile combined treatment accelerates lipid mobilization in the adipose tissue, thereby releasing more free fatty acids that are transported into hepatocytes by CD36 and further aggravate hepatic steatosis.