American Diabetes Association

TABLE 1

Liver and plasma metabolic parameters in mice fed standard diet or high-fat diet and treated with vehicle, FGF21, and rosiglitazone

Parameters	Standard diet	High-fat diet
		Vehicle	Vehicle	FGF21					Rosiglitazone
		Vehicle	Vehicle			0.1 mg/kg	1 mg/kg	10 mg/kg	Rosiglitazone
Body weight (g)^*	32.6 ± 1.2^†	49.1 ± 0.8	51.2 ± 0.9	46.1 ± 1.1	38.0 ± 1.0^†	56.2 ± 2.1^†
Liver weight (g)^*	1.5 ± 0.1^†	2.5 ± 0.2	1.9 ± 0.2	1.5 ± 0.11^†	1.2 ± 0.5^†	2.9 ± 0.14
Liver triglyceride (mg/g)^*	10 ± 2.5^†	154 ± 13.4	103 ± 27.5^‡	47 ± 2.5^†	23 ± 1.5^†	212 ± 6.6^§
Liver cholesterol (mg/g)^*	1.6 ± 0.1^†	6.4 ± 1.0	4.1 ± 1.0^‡	1.6 ± 0.1^†	1.7 ± 0.1^†	6.7 ± 0.5
Gastrocnemic muscle weight (g)^*	0.36 ± 0.01	0.38 ± 0.02	0.39 ± 0.01	0.37 ± 0.01	0.35 ± 0.01	0.37 ± 0.01
Muscle triglyceride (mg/g)^*	16 ± 1.7^†	65 ± 6.6	64 ± 11	60 ± 7.5	37 ± 4.6^‡	90 ± 15
Muscle cholesterol (mg/g)^*	1.1 ± 0.06	1.7 ± 0.4	1.7 ± 0.4	1.3 ± 0.07	1.1 ± 0.05	2.1 ± 0.4
Plasma ALT (units/l)^¶	25 ± 2.6^†	248 ± 69.7	82 ± 16.6^§	44 ± 4.5^†	30 ± 5.4^†	142 ± 32.7^‡
Plasma AST (units/l)^¶	49 ± 4.6^†	205 ± 48	102 ± 17^§	81 ± 6.5^†	69 ± 7.6^†	128 ± 17.6^‡
Plasma ALP (units/l)^¶	54 ± 1.5^‡	71 ± 8.7	45 ± 3.1^§	33 ± 3.8^†	30 ± 2^†	81 ± 7.2
Plasma glucagon (pg/ml)^¶	305 ± 88	280 ± 63	379 ± 118	204 ± 33	236 ± 35	250 ± 48
Plasma β-hydroxyburate (nmol/l)^*	0.62 ± 0.07^§	0.85 ± 0.05	0.84 ± 0.04	0.58 ± 0.06^§	0.61 ± 0.05^§	0.56 ± 0.05^§

Parameters	Standard diet	High-fat diet
		Vehicle	Vehicle	FGF21					Rosiglitazone
		Vehicle	Vehicle			0.1 mg/kg	1 mg/kg	10 mg/kg	Rosiglitazone
Body weight (g)^*	32.6 ± 1.2^†	49.1 ± 0.8	51.2 ± 0.9	46.1 ± 1.1	38.0 ± 1.0^†	56.2 ± 2.1^†
Liver weight (g)^*	1.5 ± 0.1^†	2.5 ± 0.2	1.9 ± 0.2	1.5 ± 0.11^†	1.2 ± 0.5^†	2.9 ± 0.14
Liver triglyceride (mg/g)^*	10 ± 2.5^†	154 ± 13.4	103 ± 27.5^‡	47 ± 2.5^†	23 ± 1.5^†	212 ± 6.6^§
Liver cholesterol (mg/g)^*	1.6 ± 0.1^†	6.4 ± 1.0	4.1 ± 1.0^‡	1.6 ± 0.1^†	1.7 ± 0.1^†	6.7 ± 0.5
Gastrocnemic muscle weight (g)^*	0.36 ± 0.01	0.38 ± 0.02	0.39 ± 0.01	0.37 ± 0.01	0.35 ± 0.01	0.37 ± 0.01
Muscle triglyceride (mg/g)^*	16 ± 1.7^†	65 ± 6.6	64 ± 11	60 ± 7.5	37 ± 4.6^‡	90 ± 15
Muscle cholesterol (mg/g)^*	1.1 ± 0.06	1.7 ± 0.4	1.7 ± 0.4	1.3 ± 0.07	1.1 ± 0.05	2.1 ± 0.4
Plasma ALT (units/l)^¶	25 ± 2.6^†	248 ± 69.7	82 ± 16.6^§	44 ± 4.5^†	30 ± 5.4^†	142 ± 32.7^‡
Plasma AST (units/l)^¶	49 ± 4.6^†	205 ± 48	102 ± 17^§	81 ± 6.5^†	69 ± 7.6^†	128 ± 17.6^‡
Plasma ALP (units/l)^¶	54 ± 1.5^‡	71 ± 8.7	45 ± 3.1^§	33 ± 3.8^†	30 ± 2^†	81 ± 7.2
Plasma glucagon (pg/ml)^¶	305 ± 88	280 ± 63	379 ± 118	204 ± 33	236 ± 35	250 ± 48
Plasma β-hydroxyburate (nmol/l)^*	0.62 ± 0.07^§	0.85 ± 0.05	0.84 ± 0.04	0.58 ± 0.06^§	0.61 ± 0.05^§	0.56 ± 0.05^§

Data are means ± SE. DIO mice were treated with recombinant murine FGF21 intraperitoneally at doses of 0 (vehicle), 0.1, 1, or 10 mg · kg⁻¹ · day⁻¹. An additional group of DIO mice was treated with rosiglitazone formulated in the high-fat diet to provide a dose of ∼4 mg · kg⁻¹ · day⁻¹. Mice on normal standard diet were included as controls and were injected intraperitoneally with vehicle.

Measurements that were conducted on day 42 (n = 5/group) or day 24 (n = 10/group) after the initiation of the treatments, respectively.

‡

P < 0.05,

P < 0.01,

†

P < 0.001 vs. vehicle-treated DIO mice.

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