Fig 1.
GQ-16 treatment reduces diet-induced weight gain and visceral adipose tissue mass despite increasing energy intake.
(A) Body weight gain, (B) epididymal (epiWAT) fat pad mass, (C) inguinal (ingWAT) fat pad mass, (D) energy intake, (E) metabolic efficiency and (F) daily water intake after treatment with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 m/kg/d) for two weeks. Visceral adiposity was expressed as the ratio of visceral fat weight to body weight. Subcutaneous adiposity was expressed as the ratio of subcutaneous fat weight to body weight. Data are presented as mean ± SEM. Statistical analysis was done using ANOVA followed by Newman-Keuls post hoc test. * p < 0.05 vs control diet group that received vehicle, # p < 0.05 vs HFD group that received vehicle, + p < 0.05 vs HFD that received rosiglitazone, & p < 0.05 vs all other groups. n = 4 animals per group.
Table 1.
Effects of two week-GQ-16 treatment on serum blood glucose, lipid profile and transaminases in male Swiss mice.
Fig 2.
GQ-16 treatment reduces hepatic triglyceride accumulation.
(A) Sections of liver specimens stained with hematoxylin-eosin (representative pictures with magnification x10; scale bar, 50 μm) and (B) liver triglyceride content after treatment with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 m/kg/d) for two weeks. Data are presented as mean ± SEM. Statistical analysis was done using ANOVA followed by Newman-Keuls post hoc test. & p < 0.05 vs all other groups. n = 4 animals per group.
Fig 3.
GQ-16 treatment reduces white adipocyte size.
(A) Sections of visceral white adipose tissue (epiWAT, left panel) and subcutaneous white adipose tissue (ingWAT, right panel) stained with hematoxylin-eosin (images are shown at 10x magnification. Scale bar, 100 μm) and diameter of adipocytes in (B) epiWAT and (C) ingWAT obtained from mice after treatment with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 m/kg/d) for two weeks. Data are given as mean ± SEM. Statistical analysis was done using ANOVA followed by Newman-Keuls post hoc test. * p < 0.05 vs control diet group that received vehicle, # p < 0.05 vs HFD group that received vehicle, + p < 0.05 vs HFD that received rosiglitazone. n = ~ 4 animals per group.
Fig 4.
GQ-16 reduces brown adipose tissue mass and adipocyte diameter.
(A) Interscapular brown adipose tissue (iBAT) fat pad mass, (B) gross appearance of iBAT, (C) sections of iBAT stained with hematoxylin-eosin (images are shown at 10x magnification; scale bar, 50 μm) and (D) mean diameter of brown adipocytes obtained from mice after treatment with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 m/kg/d) for two weeks. Data are given as mean ± SEM. Statistical analysis was done using ANOVA followed by Newman-Keuls post hoc test. + p < 0.05 vs HFD that received rosiglitazone; * p < 0.05 vs control diet group that received vehicle, # p < 0.05 vs HFD that received RSG or vehicle.
Fig 5.
GQ-16 treatment induces the expression of thermogenesis-related genes in brown and white adipose tissue.
Relative mRNA expression for (A, F, L) Ucp-1, (B, G, M) Cidea, (C, H, N) Prdm16, (D, I, O) Cd40, (E, J, P) Tmem26 in iBAT, epiWAT and ingWAT in mice treated with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 m/kg/d) for two weeks. Gene expression in the iBAT, epiWAT and ingWAT was determined using qRT-PCR and normalized to levels of Gapdh. Data are given as mean ± SEM. Statistical analysis was done using non-parametric Kruskal-Wallis test followed by Dunn´s test post hoc. * p < 0.05 vs HFD group that received vehicle. n = 4 animals per group. iBAT, interscapular brown adipose tissue; ingWAT inguinal white adipose tissue; epiWAT epididymal white adipose tissue.
Fig 6.
GQ-16 treatment increases UCP-1 expression in interscapular brown adipose tissue.
UCP-1 immunostaining in sections of interscapular brown adipose tissue (iBAT) obtained from mice after treatment with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 mg/kg/d) for two weeks. Representative Images (three total images per group) are shown at 20x magnification, scale bar, 50 μm. Slides were stained with NovaRED substrate that produces a red-stain in UCP-1 protein and they were counterstained with hematoxylin that results in blue-violet staining of nuclei.
Fig 7.
GQ-16 treatment induces UCP-1 expression in visceral white adipose tissue.
UCP-1 immunostaining in sections of epididymal white adipose tissue (epiWAT) obtained from mice after treatment with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 mg/kg/d) for two weeks. Representative Images (three total images per group) are shown at 10x magnification, scale bar, 50 μm. Slides were stained with NovaRED substrate that produces a red-stain in UCP-1 protein and they were counterstained with hematoxylin that results in blue-violet staining of nuclei.
Fig 8.
GQ-16 treatment induces UCP-1 expression in subcutaneous white adipose tissue.
UCP-1 immunostaining in sections of inguinal white adipose tissue (ingWAT) obtained from mice after treatment with vehicle, rosiglitazone (RSG, 4 mg/kg/d), or QG-16 (40 mg/kg/d) for two weeks. Representative Images (three total images per group) are shown at 10x magnification, scale bar, 50 μm. Slides were stained with NovaRED substrate that produces a red-stain in UCP-1 protein and they were counterstained with hematoxylin that results in blue-violet staining of nuclei.