Fig 1.
D-4F and L-5F did not affect body, liver and adipose tissue weight gain.
Weight of body (A), liver (B), visceral fat (C) and subcutaneous fat (D). Results are mean ± SEM (n = 8–10). *P<0.05 vs. ND; *P<0.001 vs. ND; *P<0.0001 vs. ND.
Fig 2.
D-4F and L-5F attenuate hepatic triglyceride accumulation.
Hepatic triglyceride (A), serum triglyceride (B) and serum NEFA (C). Results are mean ± SEM (n = 8–10). †P<0.05 vs. ND; *P<0.05 vs. HFD.
Fig 3.
D-4F and L-5F decrease hepatic mRNA levels of genes involved in lipogenesis.
Quantitative real-time PCR of key genes involved in lipogenesis (A) SREBP-1c and (B) ChREBP. mRNA levels were normalized to Ubiquitin C (UBC). Results are mean ± SEM (n = 8–10). †P<0.001 vs. ND; **P<0.001 vs. HFD.
Fig 4.
D-4F and L-5F improves blood glucose.
Beginning at 6 weeks of age, C57BL/6 mice were fed a standard chow diet (ND) or high-fat diet for a total of 16 weeks. After 10 weeks, the high fat diet group was subdivided: HFD+endotoxin-free saline (HFD); HFD+D-4F (D-4F) or HFD+L-5F (L-5F) for the last 6 weeks of diet. Plasma glucose concentrations during intraperitoneal glucose tolerance test (GTT; glucose 2g/kg) (A) before treatment commenced and (B) after 4 weeks of treatment with the mimetic peptides. (C and D) Area under the curve for glucose (AUC glucose) was calculated using the trapezoid rule. Results are mean ± SEM (n = 8–10). †P<0.05 vs. ND; *P<0.05 vs. HFD.
Fig 5.
D-4F normalizes insulin levels.
Beginning at 6 weeks of age, C57BL/6 mice were fed a standard chow diet (ND) or high-fat diet for a total of 16 weeks. After 10 weeks, the high fat diet group was subdivided: HFD+endotoxin-free saline (HFD); HFD+D-4F (D-4F) or HFD+L-5F (L-5F) for the last 6 weeks of diet. (A) Serum insulin levels were measured at various timepoints during the intraperitoneal glucose tolerance test (GTT; glucose 2g/kg). (B) Area under the curve for glucose (AUC glucose) was calculated using the trapezoid rule. Results are mean ± SEM (n = 4–6). †P<0.05 vs. ND; *P<0.05 vs. HFD.
Fig 6.
D-4F and L-5F improves insulin sensitivity.
Beginning at 6 weeks of age, C57BL/6 mice were fed a standard chow diet (ND) or high-fat diet for a total of 16 weeks. After 10 weeks, the high fat diet group was subdivided: HFD+endotoxin-free saline (HFD); HFD+D-4F (D-4F) or HFD+L-5F (L-5F) for the last 6 weeks of diet. Plasma glucose concentrations during intraperitoneal insulin tolerance test (ITT; insulin 0.5 IU/kg) (A) before treatment commenced and (B) after 5 weeks of treatment with the mimetic peptides. (C and D) Area under the curve for glucose (AUC glucose) was calculated using the trapezoid rule. Results are mean ± SEM (n = 8–10). †P<0.05 vs. ND; *P<0.05 vs. HFD.
Fig 7.
D-4F and L-5F decrease hepatic mRNA level of genes involved in gluconeogenesis.
RT-qPCR of gluconeogenic enzymes (A) PEPCK and (B) G6Pase. mRNA levels were normalized to Ubiquitin C (UBC). Results are mean ± SEM (n = 8–10). †P<0.05 vs. ND; ††P<0.001 vs. ND; **P<0.001 vs. HFD.
Fig 8.
D-4F and L-5F decrease hepatic mRNA level of genes involved in inflammation.
RTqPCR of genes involved in inflammation in the liver. mRNA levels were normalized to Ubiquitin C (UBC). Results are mean ± SEM (n = 8–10). †P<0.05 vs. ND; ††P<0.001 vs. ND; **P<0.001 vs. HFD; ***P<0.0001 vs. HFD.
Fig 9.
D-4F and L-5F decrease hepatic mRNA levels of monocyte-macrophage markers.
RTqPCR of monocyte-macrophage markers in the liver. mRNA levels were normalized to Ubiquitin C (UBC). Results are mean ± SEM (n = 8–10). ††P<0.001 vs. ND; **P<0.001 vs. HFD.