Rodent models and metabolomics in non-alcoholic fatty liver disease: What can we learn?

Table 1 Summary of existing rodent models of non-alcoholic fatty liver disease

Rodent models	Obesity	Insulin resistance	Steatosis	NASH	Fibrosis	HCC
Dietary
Deficient diet
MCD	No	Hepatic IR	Yes	Yes	Yes	No
CDAA	No	No	Yes	Yes	Yes	Yes
High-amount diet
HFD	Yes	Yes	Yes	Yes	Yes	No
HFHS	Yes	Yes	Yes	Yes	Yes	No
High fructose diet	No	Yes	Yes	No	No	No
HFHC	Yes	Yes	Yes	Yes	Yes	No
Atherogenic diet (cholesterol + cholate)	No	Hepatic IR	Yes	Yes	Yes	No
Cafeteria diet or Western diet	Yes	Yes	Yes	Yes	No	-
ALIOS	Yes	Yes	Yes	Yes	Yes	Yes
AMLN	Yes	Yes	Yes	Yes	Yes	No
DIAMOND	Yes	Yes	Yes	Yes	Yes	Yes
Genetic
ob/ob	Yes	Yes	Yes	No	No	No
db/db	Yes	Yes	Yes	No	No	No
KK-Ay	Yes	Yes	Yes	No	No	No
foz/foz	Yes	Yes	Yes	No	No	No
fa/fa	Yes	Yes	Yes	No	No	No
PTEN knockout	No	No	Yes	Yes	Yes	Yes
PPAR-α knockout	No	No	Yes	No	No	No
SREBP-1c transgenic	No	Yes	Yes	No	No	No
Chemicals
Tetracycline	No	No	Yes	Yes	Yes	-
CCl4	No	No	Yes	Yes	Yes	Yes
TAA	-	-	Yes	Yes	Yes	Yes
STZ	-	-	-	Yes	-	-
DMN	-	-	No	Yes	Yes	Yes
DEN	No	-	Yes	Yes	Yes	Yes
Porphyrinogenic agents (DDC or GF)	-	-	Yes	Yes	-	-
MSG	Yes	Yes	Yes	Yes	No	Yes
Tunicamycin	-	-	Yes	Yes	-	-
Surgical
CBDL	-	-	Yes	Yes	Yes	-
Combined models
ob/ob + MCD diet	Yes	-	Yes	Yes	No	No
db/db + MCD diet	Yes	Yes	Yes	Yes	Yes	No
HFD + thermoneutral housing at 30 ºC	-	-	-	Yes	Yes	-
HFD + CCl4	No	-	Yes	Yes	Yes	Yes
HFD + DEN	Yes	-	Yes	Yes	Yes	Yes
CDAA + CCl4	No	-	Yes	Yes	Yes	Yes
STAM model	No	-	Yes	Yes	Yes	Yes

ALIOS: American lifestyle-induced obesity syndrome model (high-fat + trans-fat + fructose); AMLN: Amylin liver NASH model; CBDL: Common bile duct ligation; CCl₄: Carbon tetrachloride; CDAA: Choline-deficient, L-amino defined diet; DDC: 3,5-diethoxycarbonly-1,4-dihydrocollidine; DEN: Diethylnitrosamine; DIAMOND: Diet-induced animal model of non-alcoholic fatty liver disease mice; DMN: Dimethylnitrosamine; GF: Griseofulvin; HCC: Hepatocellular carcinoma; HFD: High-fat diet; HFHC: High-fat high-cholesterol diet; HFHS: High-fat high-sugars diet (mainly fructose or sucrose); MCD: Methionine and choline deficient diet; MSG: Monosodium glutamate; NASH: Non-alcoholic steatohepatitis; STZ: Streptozotocin; STAM: Stelic animal model of NASH (STZ + HFD); TAA: Thioacetamide.

Table 2 Studies related to “non-alcoholic steatohepatitis”, “rodent models” and “metabolomics”

Rodent model	Produced by	Animals used	Biological sample	Platform used	Ref.
Dietary	HFD	C57BL/6 mice. 6-wk-old	Liver extract and serum	UPLC-QTOF-MS and GC-MS	Kim et al[94]
	HFD and Paigen diet	BALB/c mice. 6-wk-old	Liver extract and urine	1H-NMR	Klein et al[95]
	HFD and HCD	C57BL/6N mice. 6-wk-old	Urine	1H-NMR	Jung et al[96]
	HFD and HCD	Wistar rats. 6-wk-old	Liver extract	1H-NMR	Bertram et al[97]
	HFD	C57BL/6S1ac mice. 4-wk-old	Urine	1H-NMR and UPLC-QTOF-MS	Li et al[98]
	HFD	C57BL/6J mice. 6-wk-old	Serum	UHPLC-QTOF-MS and GC-MS	Lai et al[99]
	High-fructose and saturated fatty acid diet	Sprague-Dawley rats	Liver extract	HR-MAS and 1H-NMR	Tranchida et al[100]
	HFHCC diet	C57BL/6J mice. 8-wk-old	Liver extract and plasma	GC-TOF MS and CSH-QTOF MS	Tu et al[101]
	HFD	Sprague-Dawley rats. 4-6-wk-old	Liver extract	LC-MS	Wan et al[102]
	HFD	Sprague-Dawley. 6-wk-old	Urine and feces	1H-NMR	Chen et al[103]
	MCD	C57BL/6J mice. 8-wk-old	Feces	GC-MS	Ye et al[104]
	HFD	Swiss albino mice	Serum and feces	1H-NMR	Carvalho et al[105]
	High fat-sucrose diet	Sprague-Dawley rats. 6-wk-old	Serum	HPLC-QTOF-MS	Xu et al[106]
	MCD and atherogenic diet	C57BL/6J mice. 10-wk-old	Liver extract	MS	Montandon et al[107]
	HFD	Sprague-Dawley rats. 6-8-wk-old	Serum	LC-MS	Cui et al[108]
	HFD	Sprague-Dawley, Fisher 344 and Brown-Norway rats. 5-wk-old	Liver extract	LC-MS	Boyce et al[109]
Genetic	Db/db mice	C57BL/6J mice. 10-wk-old	Liver extract	1H-NMR and UPLC-QTOF-MS	Kim et al[110]
	Ob/ob mice	B6.Cg-Lepob/J mice. 8-wk-old	Liver extract	HR-MAS and1H-NMR	Gogiashvili et al[111]
Chemical	DEN	Sprague-Dawley rats. 4-wk-old	Liver extract	1H-NMR	Wang et al[112]
	CCl4	Wistar rats	Plasma	UPLC-QTOF-MS	Li et al[113]
	CCl4	Sprague-Dawley rats. 4-wk-old	Urine	GC-TOF MS	Jiang et al[114]
	CCl4	Wistar rats	Liver extract	GC-MS	Song et al[115]
	CCl4	Sprague-Dawley rats	Urine	1H-NMR	Wu et al[116]
	CCl4	Wistar rats	Urine	GC-MS	Fang et al[117]
	CCl4	Sprague-Dawley rats. 1-yr-old	Serum and urine	UPLC-QTOF-MS	Chang et al[118]
	CCl4	Sprague-Dawley rats. 7-wk-old	Serum	1H-NMR	Li et al[119]
	CCl4	Sprague-Dawley rats	Serum	1H-NMR	Liu et al[120]
	DEN	Sprague-Dawley rats. 6-wk-old	Serum	1H-NMR	Yang et al[121]
Combined model	Combined (genetic + dietary) with HCD	Acyl knockouts mice on a C57BL6/J background. 4-wk-old	Serum	LC-MS	Zhao et al[122]

CCl₄: Carbon tetrachloride; CSH-QTOF MS: Reverse-phase lipid chromatography-quadrupole/time-of-flight mass spectrometry; DEN: Diethylnitrosamine; GC-MS: Gas chromatography-mass spectrometry; GC-TOF MS: Gas chromatography-time-of-flight mass spectrometry; HCD: High-carbohydrate diet; HFD: High-fat diet; HFHCC: High-fat, high cholesterol, cholate diet; HPLC-QTOF-MS: High-performance liquid chromatography quadrupole time of flight mass spectrometry; ¹H-NMR: Proton nuclear magnetic resonance; LC-MS: Liquid chromatography-mass spectrometry; MCD: Methionine, and choline-deficient diet; MS: Mass spectroscopy; UPLC-QTOF-MS: Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.