Prevention and treatment effect of evogliptin on hepatic steatosis in high-fat-fed animal models.

Abstract

Dipeptidyl peptidase 4 (DPP4) is an adipokine that interrupts insulin signaling. The resulting insulin resistance exacerbates hepatic steatosis. We previously reported that the novel DPP4 inhibitor evogliptin improves insulin resistance. This study aimed to verify the therapeutic potential of evogliptin for fatty liver. Evogliptin treatment was initiated simultaneously with a high-fat diet (HFD) feeding in normal mice and in a post-24 week HFD-fed rats. In a prevention study, insulin sensitivity was preserved in evogliptin-treated mice after a 16-week treatment. Overall plasma lipid levels stayed lower and hepatic lipid accumulation was drastically suppressed by evogliptin treatment. Evogliptin reduced hepatic expression of Srebf1, a key transcriptional factor for lipogenesis. Additionally, DPP4 inhibitor-treated mice showed less weight gain. In a treatment study, after evogliptin treatment for 14 weeks in pre-established HFD-fed obese rats, weight loss was marginal, while hepatic lipid accumulation and liver damage assessed by measuring plasma aminotransferase levels were completely resolved, suggesting weight loss-independent beneficial effects on fatty liver. Moreover, reduction in plasma non-esterified fatty acids supported the improvement of insulin resistance by evogliptin treatment. Conclusively, our findings suggest that evogliptin treatment ameliorates fatty liver by increasing insulin sensitivity and suppressing lipogenesis.

• Authors: Mi-Kyung Kim, Yu Na Chae, Gook-Jun Ahn, Chang Yell Shin, Song-Hyen Choi, Eun Kyoung Yang, Yong Sung Sohn, Moon-Ho Son
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 40 Issue 2 Pg. 268-281 (Feb 2017) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 27885461 (Publication Type: Journal Article)

Chemical References

• 4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one
• Blood Glucose
• Dipeptidyl-Peptidase IV Inhibitors
• Piperazines
• Triglycerides
• Alanine Transaminase
• DPP4 protein, rat
• Dipeptidyl Peptidase 4
• Dpp4 protein, mouse

Topics

• Alanine Transaminase (blood)
• Animals
• Blood Glucose
• Diet, High-Fat (adverse effects)
• Dipeptidyl Peptidase 4 (metabolism)
• Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)
• Disease Models, Animal
• Fatty Liver (blood, drug therapy, prevention & control)
• Insulin Resistance
• Lipogenesis (drug effects)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Piperazines (therapeutic use)
• Rats
• Rats, Wistar
• Triglycerides (blood)
• Weight Gain (drug effects)