Role of pentoxifylline in non-alcoholic fatty liver disease in high-fat diet-induced obesity in mice

Table 1 Diet composition

	Control (AIN-93)		HFD
	g/kg	kcal/kg	g/kg	kcal/kg
Cornstarch (QSP)	397.5	1590	1155	462
Casein	200	800	200	800
Sucrose	100	400	100	400
Dextrinated starch	132	528	132	528
Soybean oil	70	630	40	360
Lard	-	-	312	2808
Cellulose	50	-	50	-
Mineral mix	35	-	35	-
Vitamin mix	10	-	10	-
L-cystine	3	-	3	-
Choline	2.5	-	2.5	-
Total	1000	3948	1000	5358

HFD: High-fat diet.

Table 2 Metabolic and anthropometric parameters of lean (control) and obese (high-fat diet) mice treated with pentoxifylline

	Control		HFD
	NT	PTX	NT	PTX
Final BW (g)	34.2 ± 1.0	37.0 ± 2.0	51.6 ± 1.5a	52.0 ± 2.7
Liver (g)	1.7 ± 0.2	1.7 ± 0.0	2.6 ± 0.2a	1.7 ± 0.0c
Liver (% of BW)	4.1 ± 0.0	4.6 ± 0.1c	4.8 ± 0.2a	3.3 ± 0.0c
Visceral adipose tissue (g)	0.8 ± 0.1	0.9 ± 0.2	1.8 ± 0.2a	2.7 ± 0.1c
Visceral adipose tissue (% of BW)	2.2 ± 0.2	2.4 ± 0.4	3.4 ± 0.3a	5.4 ± 0.4c
Blood glucose (mg/dL)	120.6 ± 6.8	131.0 ± 3.0	178.6 ± 10a	141.0 ± 16
kITT	4.0 ± 0.6	3.6 ± 0.3	2.1 ± 0.1a	1.6 ± 0.3
Insulin (ng/mL)	0.4 ± 0.1	0.4 ± 0.2	4.4 ± 2.0a	4.5 ± 1.2
AST (U/L)	19.4 ± 4.6	9.4 ± 2.3a	23.2 ± 6.9	12.1 ± 1.6c
ALT (U/L)	3.12 ± 0.9	9.0 ± 2.0a	2.25 ± 0.9	4.2 ± 1.5

^aP < 0.05 vs control NT group;

^cP < 0.05 vs paired NT group. HFD: High-fat diet; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; PTX: Pentoxifylline; BW: Body weight; NT: Non-treated; kITT: Rate constant for glucose disappearance during an insulin tolerance test.

Table 3 Liver histological score of lean (control) and obese (high-fat diet) mice treated with pentoxifylline

	Control		HFD
	NT	PTX	NT	PTX
Macrosteatosis	0 (0-0)	0 (0-0)	2.0 (1-3)	2.0 (2-3)
Microsteatosis	0 (0-0)	0 (0-0)	1.8 (1-3)	1.3 (1-2)a
Hyperemia	0 (0-0)	0 (0-0)	0.8 (0-1)	0.3 (0-1)a
Inflammation	0 (0-0)	0 (0-0)	0.6 (0-1)	0.3 (0-1)c
Fibrosis	0 (0-0)	0 (0-0)	0 (0-0)	0 (0-0)

^aP = 0.06;

^cP < 0.05 vs the matched NT group. HFD: High-fat diet; NT: Non-treated; PTX: Pentoxifylline.

Table 4 Hepatic cytokines in lean (control) and obese (high-fat diet) mice treated with pentoxifylline

	Control		HFD
	NT	PTX	NT	PTX
TNF-α (pg/mL)	29.6 ± 6.6	75.4 ± 12.6c	156.3 ± 17.2a	62.6 ± 7.6c
IL-10 (pg/mL)	27.2 ± 3.6	37.3 ± 8.3	27.5 ± 5.2	29.4 ± 8.2
MCP-1 (pg/mL)	34.9 ± 4.9	56.2 ± 12.3	89.1 ± 10.8a	112.3 ± 22.4

^aP < 0.05 vs control NT group;

^cP < 0.05 vs the matched NT group. HFD: High-fat diet; NT: Non-treated; PTX: Pentoxifylline; TNF-α: Tumor necrosis factor α; IL-10: Interleukin-10; MCP: Monocyte chemoattractant protein-1.

Table 5 Adipokine profile of lean (control) and obese (high-fat diet) mice treated with pentoxifylline

	Control		HFD
	NT	PTX	NT	PTX
TNF-α (pg/mL)	87.2 ± 2.8	75.5 ± 3.9	106.1 ± 17.6	51.1 ± 9.6c
IL-6 (pg/mL)	227.9 ± 23.3	178.5 ± 30.9	340.8 ± 51.3	166.6 ± 22.5c
PAI-1 (pg/mL)	600.2 ± 32.3	1508.6 ± 210.4c	2646.3 ± 755.1a	4434.5 ± 1400.1
MCP-1 (pg/mL)	287.8 ± 17.1	253.8 ± 13.3	721.5 ± 112.8a	563.8 ± 109.7
Leptin (ng/mL)	8.1 ± 0.7	23.1 ± 2.9c	26.6 ± 3.0a	20.5 ± 3.7
Adiponectin (ng/mL)	109.1 ± 0.5	102.8 ± 0.6	106.8 ± 1.7	102.8 ± 5.9

^aP < 0.05 vs control NT group;

^cP < 0.05 vs the matched NT group. HFD: High-fat diet; NT: Non-treated; PTX: Pentoxifylline; TNF-α: Tumor necrosis factor α; IL-6: Interleukin-6; MCP: Monocyte chemoattractant protein-1; PAI: Plasminogen activator inhibitor-1.