Melatonin attenuates high fat diet-induced fatty liver disease in rats

Table 1 Univariate analysis of diet and melatonin use and its duration

	Liver weight (g)	P value	Liver weight/body weight (%)	P value	Portal vein pressure (mmHg)	P value
Diet
HFD	13.3 ± 2.8	< 0.001	3.5 ± 0.5	< 0.001	11.9 ± 2.7	< 0.001
RD	9.1 ± 1.3	BV	2.4 ± 0.3	BV	8.0 ± 1.7	BV
Melatonin
10 mg/kg	11.2 ± 2.5	< 0.001	3.0 ± 0.5	< 0.001	10.5 ± 2.6	0.01
5 mg/kg	11.3 ± 2.3	< 0.001	3.0 ± 0.6	< 0.001	10.3 ± 2.8	0.03
0 mg/kg	16.2 ± 2.3	BV	4.0 ± 0.5	BV	13.0 ± 3.5	BV
Duration
8 wk	12.0 ± 3.6	0.86	3.2 ± 0.7	0.71	10.1 ± 2.5	0.02
4 wk	12.2 ± 2.6	BV	3.2 ± 0.7	BV	12.0 ± 3.3	BV

Variables are expressed as mean ± SD. HFD: High fat diet; RD: Regular diet; BV: Baseline value.

Table 2 Effect of melatonin after adjusting for high fat diet and duration of its use

Melatonin	5 mg/kg	P value	10 mg/kg	P value
Liver weight (g)	-3.9	< 0.001	-3.9	< 0.001
Liver weight/body weight ratio (%)	-0.7	< 0.001	-0.7	< 0.001
Portal vein pressure (mmHg)	-1.6	0.09	-1.4	0.14

Results are expressed as the mean difference between rats on melatonin by comparison to those not on melatonin.

Table 3 Univariate analysis of diet, melatonin use and its duration n (%)

n = 68	Grade 0	Grade 1	Grade 2	Grade 3	OR (95%CI)	P value
Diet
HFD (n = 48)	1 (2.10)	19 (39.60)	12 (25)	16 (33.30)	NE	< 0.001
RD (n = 20)	20 (100)	0 (0)	0 (0)	0 (0)	BV
Melatonin
10 mg/kg (n = 29)	11 (37.90)	9 (31)	8 (27.60)	1 (3.40)	0.851 (0.72-0.99)	0.04
5 mg/kg (n = 27)	10 (37)	10 (37)	4 (14.90)	3 (11.10)
0 mg/kg (n = 12)	0 (0)	0 (0)	0 (0)	12 (100)
Duration
8 wk (n = 35)	11 (31.40)	10 (28.60)	7 (20)	7 (20)	0.95 (0.34-2.66)	0.92
4 wk (n = 33)	10 (30.30)	9 (27.30)	5 (15.10)	9 (27.30)	BV

¹Per 1 mg/kg increase in melatonin. HFD: High fat diet; NE: Not estimated; RD: Regular diet; BV: Baseline value.

Table 4 Ordinal logistic regression analysis of melatonin effect in rats on high fat diet

n = 48	OR (95%CI)	P value
Melatonin (per 1 mg/kg increase)	0.69 (0.59-0.83)	< 0.001
Duration (8 wk vs 4 wk)	0.65 (0.20-2.10)	0.47

Table 5 Effect of melatonin on laboratory indices

	Melatonin (5 mg/kg)	P value	Melatonin (10 mg/kg)	P value
Lipidemic profile
TC (mg/dL)	-10.7	0.45	-2.2	0.87
LDL (mg/dL)	-6.3	0.60	-3.9	0.74
HDL (mg/dL)	-5.3	0.10	1.9	0.52
TG (mg/dL)	6.7	0.71	-5.2	0.76
Hepatic function
AST (U/L)	-170	0.01	-224	0.001
ALT (U/L)	-62.9	0.01	-93.4	< 0.001
Oxidative profile
MDA	-12.7	< 0.001	-12.2	< 0.001
GSH	20.1	0.004	29.2	< 0.001

Multivariate linear regression analysis of melatonin effect after adjusting for duration of its use and high fat diet (HFD). Results are expressed as the mean difference between rats on melatonin by comparison to those not on melatonin. TC: Total cholesterol; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; TG: Triglycerides; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; MDA: Malondialdehyde; GSH: Glutathione.