Table 1.
Study design.
Fig 1.
Body weight-loss effect of DPP4 inhibitors in established obese mice after 4-week treatment.
(A) To select each dosage for twice daily administration, plasma DPP4 inhibition was assessed 12 h after a single oral administration in HF-DIO mice. (B-E) After 4 week-administration of evogliptin, sitagliptin, vildagliptin, saxagliptin, or linagliptin twice daily by oral gavage in HF-DIO mice, (B) body weight, (C) fed plasma levels of active GLP-1, (D) insulin, and (E) fed blood glucose levels were determined (n = 5/group). #, P < 0.05 vs. lean control; *, P < 0.05 vs. HF-DIO control by one-way ANOVA; †, P < 0.05 vs. the baseline by RM two-way ANOVA.
Fig 2.
Two-week treatment of evogliptin decreased whole body fat mass in obese mice.
After HF-DIO mice were treated with exenatide (30 μg kg-1, once daily, s.c.) or evogliptin at 0.027%, 0.081%, or 0.27% (w/w) for 2 weeks, (A) plasma DPP4 activity, (B) body weight, (C) energy intake, (D) whole body fat mass, (E) lean body mass, and (F) plasma triglycerides levels were determined (n = 8/group). #, P < 0.05 vs. lean control and *, P < 0.05 vs. HF-DIO control by one-way ANOVA; †, P < 0.05 vs. the baseline by RM two-way ANOVA; ‡, P < 0.05 vs. HF-DIO control by Student’s t-test.
Fig 3.
Evogliptin treatment reduced adipocyte size and distribution.
HF-DIO mice were treated with exenatide (30 μg kg-1, once daily, s.c.) or evogliptin at 0.027%, 0.081%, or 0.27% (w/w) for 2 weeks. The effects on adipocytes from epididymal fat tissues were histologically determined (three sections/animals, eight animals/group). (A) Representative images (original magnification, ×200), (B) mean adipocyte areas and (C-D) percentile distribution of adipocyte size were presented. #, P < 0.05 vs. lean control and *, P < 0.05 vs. HF-DIO control by one-way ANOVA.
Fig 4.
Evogliptin increased energy expenditure unlike exenatide.
HF-DIO mice were treated with exenatide (30 μg kg-1, once daily, s.c.) or evogliptin at 0.081% (w/w) for 2 weeks. Metabolic parameters were measured using an indirect calorimetry system; (A) Oxygen consumption (VO2) and carbon dioxide production (VCO2), (B) mean energy expenditure (EE), (C) respiratory quotient (Rq), and (D) a plot of individual data of total mean EE vs. (lean mass + 0.2 × fat mass) as a covariate (n = 8/group). #, P < 0.05 vs. lean control and *, P < 0.05 vs. HF-DIO control by one-way ANOVA.
Fig 5.
Effects on plasma insulin and adipokines.
After 2-week treatment of exenatide (30 μg kg-1, once daily, s.c.) or evogliptin at 0.081% (w/w) in HF-DIO mice, fed plasma concentrations of (A) insulin, (B) leptin and (D) high molecular weight (HMW) adiponectin were assessed (n = 8/group). #, P < 0.05 vs. lean control and *, P < 0.05 vs. HF-DIO control by one-way ANOVA.
Fig 6.
Effect of evogliptin treatment on the gene expression in muscle and adipose tissues.
After 2–week administration of exenatide (30 μg kg-1, once daily, s.c.) or evogliptin at 0.081% (w/w) in HF-DIO mice, (A) PGC-1α (Ppargc1a) gene expression in soleus muscle and two types of fat tissues (interscapular fat and epididymal fat for brown adipose tissue and white adipose tissue, respectively), and gene expression levels of (B) UCP1 (Ucp1), (C) COXIV (Cox4i1) and HIF-1α (Hif1a) were assessed in white adipose tissue by realtime qPCR method (n = 8/group). #, P < 0.05 vs. lean control and *, P < 0.05 vs. HF-DIO control by one-way ANOVA; ‡, P < 0.05 by Student’s t-test.