Translational approaches: From fatty liver to non-alcoholic steatohepatitis

Table 1 Summary of the major findings obtained among the most widespread in vivo models

Model	Genetic manipulation	Diet modifications	Obesity	Metabolic syndrome (IR)	Hepatosteatosis	Steatohepatitis	Fibrosis
ob/ob	Leptin Deficient	No	Yes	Yes	Yes	Yes (in males)	No (protected)
mice		Yes	Variable	Yes	Yes	Yes	Yes
		MCD	(loss weight in some)
db/db	Mutation on leptin receptor	No	Yes	Yes	Yes	No	No
mice		Yes	Variable	No	Yes	Yes	Yes
		MCD	(age-related weight gain)
AOX	Nullizygous for acycil - CoA oxidase	No	No	No	Yes	Yes	No
null mice					[before 6-8 mo	(before 6-8 mo)
					Resistant	Resistant
					(after 8 mo)]	(after 8 mo)
MATO	Nullizygous for (MAT)-1A	No	No	No	Yes	Yes	Yes
null mice
pten	Liver specific pten deletion	No	No	No	Yes	Yes	Yes
null mice
(SREBP)-1c	SREBP-1c overexpressed in adipose tissue	No	No	Yes	Yes	Yes	Yes
transgenic mice
KK-Ay	Heterozygous mutation on agouti gene (KK-Ay/a)	No	Yes	Yes	Yes	No	No
mice		Yes	Yes	Yes	Yes	Yes	No
		MCD
LIRKO	Liver-specific Leptin receptor KO	No	No	Hepatic IR	No	-	-
mice
C57Bl/6J	No	Yes	Yes	Yes	Yes	Yes	Yes
		HFHC					(mild)
		HF
Cholesterol-Cholate	No	Yes	No	No	Yes	Yes	Yes
(Atherogenic diet)		Cholesterol		(only hepatic IR)	(over 1-6 mo)	(over 1-6 mo)	(over 1-6 mo)
		Cholate

MCD: Methionine choline deficient diet; HFHC: High fat-high carbohydrate diet; HF: High fructose diet; KO: Knock-out; IR: Insulin resistance.