INT-767 improves histopathological features in a diet-induced ob/ob mouse model of biopsy-confirmed non-alcoholic steatohepatitis

Table 1 Effect of 8 wk of treatment with INT-767 on metabolic parameters, non-alcoholic fatty liver disease activity score/fibrosis stage, body weight/composition, and liver weight in ob/ob-NASH mice

	Vehicle, (n = 10)	INT-767, 3 mg/kg (n = 10)	INT-767, 10 mg/kg (n = 10)
Baseline plasma ALT (U/L)	577 ± 43.4	552 ± 36.1	498 ± 27.3
Terminal plasma ALT (U/L)	670 ± 58.9	478 ± 33.9	250 ± 21.6bf
Baseline plasma AST (U/L)	436 ± 36.7	421 ± 16.7	359 ± 15.6
Terminal plasma AST (U/L)	552 ± 49.4	447 ± 38.8	257 ± 42.3ef
Baseline plasma TC (mmol/L)	10.3 ± 0.8	10.3 ± 0.8	11.1 ± 0.3
Terminal plasma TC (mmol/L)	10.7 ± 0.5	9.2 ± 0.3	7.2 ± 0.4ef
Baseline plasma TG (mmol/L)	0.8 ± 0.0	0.8 ± 0.1	0.8 ± 0.1
Terminal plasma TG (mmol/L)	0.7 ± 0.0	0.6 ± 0.0	0.6 ± 0.1
Terminal liver TC (mg/g tissue)	32.9 ± 1.7	24.0 ± 1.1d	18.0 ± 1.5f
Terminal liver TG (mg/g tissue)	233 ± 12.3	229 ± 15.4	149 ± 14.0d
Fasting blood glucose (week 4, mmol/ L)	7.6 ± 0.1	8.2 ± 0.2	8.0 ± 0.3
OGTT, glucose AUC (week 4, mmol/ L x min)	1318 ± 61	1304 ± 38	1417 ± 78
Fed blood glucose (week 8, mmol/ L)	7.1 ± 0.2	6.8 ± 0.2	7.3 ± 0.3
Fed plasma insulin (week 8, pmol/ L)	567 ± 133	482 ± 122	799 ± 229
Baseline steatosis score	3.0 ± 0.0	2.9 ± 0.1	2.9 ± 0.1
Terminal steatosis score	3.0 ± 0.0	3.0 ± 0.0	1.8 ± 0.2f
Baseline inflammation score	2.5 ± 0.1	3.0 ± 0.0	3.0 ± 0.0
Terminal inflammation score	2.3 ± 0.1	2.2 ± 0.2	1.0 ± 0.1f
Baseline ballooning degeneration score	0.6 ± 0.1	0.7 ± 0.1	0.8 ± 0.1
Terminal ballooning degeneration score	0.9 ± 0.1	0.7 ± 0.1	0.2 ± 0.1f
Baseline NAFLD activity score (NAS)	6.1 ± 0.2	6.3 ± 0.2	6.4 ± 0.2
Terminal NAFLD activity score (NAS)	6.2 ± 0.2	5.9 ± 0.2	3.0 ± 0.3f
Baseline fibrosis stage	2.7 ± 0.2	2.6 ± 0.1	2.6 ± 0.1
Terminal fibrosis stage	2.7 ± 0.1	2.5 ± 0.1	1.6 ± 0.1f
Terminal steatosis (% area)	41.1 ± 1.0	40.6 ± 1.6	24.8 ± 2.3f
Terminal fibrosis (% area)	15.9 ± 0.9	13.6 ± 0.8	8.9 ± 0.6f
Baseline BW (g)	49.8 ± 0.7	48.2 ± 1.0	49.4 ± 1.3
Terminal BW (g)	54.6 ± 0.8	52.6 ± 0.8	51.3 ± 1.8
Body weight change (%, relative to day 0)	109 ± 1.3	107 ± 2.1	103 ± 2.3
Baseline whole-body lean mass (g)	14.0 ± 0.4	14.6 ± 0.3	14.4 ± 0.4
Terminal whole-body lean mass (g)	17.3 ± 0.4	17.6 ± 0.5	17.2 ± 0.2
Baseline whole-body lean mass (% of BW)	28.2 ± 0.6	30.3 ± 0.6	29.1 ± 0.6
Terminal whole-body lean mass (% of BW)	31.9 ± 0.6	33.9 ± 0.9	33.6 ± 0.8
Baseline whole-body fat mass (g)	18.5 ± 0.4	18.5 ± 0.7	19.5 ± 0.7
Terminal whole-body fat mass (g)	22.5 ± 0.4	21.0 ± 0.7	19.3 ± 0.7e
Baseline whole-body fat mass (% of BW)	37.2 ± 0.7	38.4 ± 1.2	39.4 ± 0.6
Terminal whole-body fat mass (% of BW)	41.4 ± 0.5	40.4 ± 0.9	37.5 ± 0.7e
Terminal liver weight (g)	5.4 ± 0.2	4.9 ± 0.1	4.1 ± 0.1f
Terminal liver weight (% of BW)	9.8 ± 0.3	9.4 ± 0.2	8.0 ± 0.3d

Morphometric scores were analyzed by a χ² test compared to vehicle. All other data were analyzed by a two-way ANOVA with Bonferroni’s post-hoc test (^aP < 0.05,

^bP < 0.01,

^eP < 0.001; vs baseline. ^cP < 0.05,

^dP < 0.01,

^fP < 0.001, vs vehicle).