Article Figures & Data
Figures
- Fig. 1.
Effects of SCO-267 on glucagon and GLP-1 secretion in CDAHFD-fed mice. (A) Glucagon levels and (B) GLP-1 levels after drug dosing. SCO-267–stimulated glucagon and GLP-1 secretion in CDAHFD-fed mice. Values are presented as means ± S.D. (n = 5). †P < 0.025 and ‡P < 0.025 vs. vehicle by one-tailed Williams’ test and one-tailed Shirley-Williams test, respectively. AUC0–2 h, area under the curve from 0 to 2 hours; SCO, SCO-267; Veh, vehicle.
- Fig. 2.
Effects of repeated doses of SCO-267 on metabolic parameters in CDAHFD-fed mice. (A) Daily food intake, (B) change in body weight during the study, (C) plasma glucose, and (D) plasma triglyceride at the end of the 4-week study. Baseline body weight for CDAHFD group was 25.4 ± 1.6 g. SCO-267 did not affect food intake, body weight, plasma glucose, or plasma triglyceride levels. Values are presented as means ± S.D. (n = 8). *P < 0.05 vs. vehicle by Student’s t test. Alo, alogliptin benzoate; Dapa, dapagliflozin; SCO, SCO-267; SD, standard diet; Veh, vehicle.
- Fig. 3.
Effects of repeated doses of SCO-267 on liver parameters in CDAHFD-fed mice. (A) Liver triglyceride content, (B) liver weight, (C) liver collagen content, and (D) plasma alanine aminotransferase levels at the end of the 4-week study. SCO-267 decreased liver triglyceride content, liver weight, liver collagen content, and plasma alanine aminotransferase levels. Values are presented as means ± S.D. (n = 8). †P < 0.025 vs. vehicle by one-tailed Williams’ test. Alo, alogliptin benzoate; Dapa, dapagliflozin; SCO, SCO-267; SD, standard diet; Veh, vehicle.
- Fig. 4.
Effects of repeated doses of SCO-267 on liver TBARS levels in CDAHFD-fed mice. Liver TBARS levels at the end of the 4-week study. SCO-267 decreased liver TBARS levels. Values are presented as means ± S.D. (n = 8). ‡P < 0.025 vs. vehicle by one-tailed Shirley-Williams test. Alo, alogliptin benzoate; Dapa, dapagliflozin; SCO, SCO-267; SD, standard diet; Veh, vehicle.
- Fig. 5.
Effects of repeated doses of SCO-267 on liver mRNA levels in CDAHFD-fed mice. Liver levels of mRNAs related to (A) mitochondrial function, (B) β-oxidation pathway, (C) lipogenesis pathway, (D) inflammation pathway, (E) reactive oxygen species generation, and (F) fibrosis pathway at the end of the 4-week study. SCO-267–elevated mRNA levels of molecules with roles in mitochondrial function and β-oxidation and inhibited those with roles in lipogenesis, inflammation, reactive oxygen species generation, and fibrosis in the liver. Values are presented as means ± S.D. (n = 7 to 8). †P < 0.025 and ‡P < 0.025 vs. vehicle by one-tailed Williams’ test and Shirley-Williams test, respectively. *P < 0.05 and **P < 0.01 vs. vehicle by Student’s t test. #P < 0.05 and ##P < 0.01 vs. vehicle by Aspin-Welch test. Acadl, acyl-CoA dehydrogenase, long chain; Acta2, actin, α2, smooth muscle, aorta; Alo, alogliptin benzoate; Ccl2, chemokine (C-C motif) ligand 2; Cd36, CD36 molecule; Col1a1, collagen type 1, α1; Cybb, cytochrome b-245, β polypeptide; Dapa, dapagliflozin; Il6, interleukin-6; Ncf1, neutrophil cytosol factor 1; Ppara, peroxisome proliferator–activated receptor α; SCO, SCO-267; SD, standard diet; Srebf1, sterol regulatory element binding transcription factor 1; Tfam, transcription factor A, mitochondrial; Tgfb1, transforming growth factor β 1; Tnf, tumor necrosis factor; Veh, vehicle.
Additional Files
Data Supplement
- Supplemental Data -
Supplementary Figure 1 - Pharmacokinetic analysis of CDAHFD-fed mice.
Supplementary Figure 2 - Plasma insulin levels in CDAHFD-fed mice.
Supplementary Figure 3 - Plasma aspartate aminotransferase levels in CDAHFD-fed mice.
Supplementary Figure 4 - Liver mRNA levels of G6pc and Gys2 in CDAHFD-fed mice.
Supplementary Figure 5 - Liver mRNA levels of Ffar1.
Supplementary Table 1 - Taqman Gene Expression Assays used for qPCR.
Supplementary Table 2 - Primer sequences for SYBR green qPCR.
Supplementary Table 3 - Primers, probe, and standard sequence for mouse Ffar1.
- Supplemental Data -
In this issue
GPR40 Full Agonist for Nonalcoholic Fatty Liver Disease
