Table 1.

Recent studies using genetic animal models to investigate the role of the MAPKs in the liver

MAPK	Genetic manipulation/other strategies	Phenotype in knock-out mouse models	Hepatic MAPK expression in obesity	References
JNK1/2	Liver-specific deletion of JNK1 and JNK2 in mice	Protected from diet-induced obesity and exhibit enhanced insulin sensitivity. Activation of hepatic PPARα and its target gene FGF21.	Undetermined	[23]
JNK1	Role of JNK1 signaling in autophagy and insulin resistance in NAFLD rat model	Rats fed a high-fat diet exhibit impaired glucose tolerance and hepatic injury, hepatic insulin resistance and enhanced autophagy.	Increase expression of phosphorylated JNK1 in obesity	[27]
JNK1	Liver-specific deletion of JNK1 in mice	Reduced hepatic stellate cells derived extracellular matrix deposition and fibrosis.	Undetermined	[55]
p38α MAPK	Liver-specific p38α MAPK knock-out mice	Decreased fasting glucose and impaired gluconeogenesis associated with enhanced AMPKα phosphorylation.	Enhanced expression of p38 MAPK in obesity	[40]
p38α MAPK	Ob/ob whole body knock-out mice	Activation of p38 MAPK enhanced nuclear translocation of Xbp1s, decreased ER stress and maintained euglycemia in obese and diabetic mice.	Reduced hepatic p38 MAPK phosphorylation in ob/ob and HFD fed obese mice	[43]
p38α MAPK	Effect of p38 MAPK inhibition on free fatty acid-induced insulin resistance in rats	Inhibition of p38 MAPK blocked lipid-induced hepatic insulin resistance and is associated with attenuated activation of ATF2	Undetermined	[45]
ERK1	Ob/ob/ERK1 whole body double knock-out mice	Enhanced whole body insulin sensitivity, partially protected against hepatosteatosis	Undetermined	[54]
ERK2	ERK2 liver-specific knock-out mice	High-fat/high-fructose diet fed ERK2 liver-specific KO mice exhibit hepatic steatosis, glucose intolerance and reduced insulin sensitivity.	No increase in hepatic ERK phosphorylation in obesity	[48]
ERK1	ERK1 whole body knock- out mice	Decreased adiposity and are resistant to diet-induced obesity and insulin resistance.	No increase in hepatic ERK phosphorylation in obesity	[46]
ERK1	ERK1 whole body knock- out	Increased weight gain and increased insulin resistance in diet- induced obesity	Increase in ERK2 phosphorylation in obesity	[47]