TY  - JOUR
A1  - Spruss, Astrid
A1  - Henkel, Janin
A1  - Kanuri, Giridhar
A1  - Blank, Daniela
A1  - Püschel, Gerhard Paul
A1  - Bischoff, Stephan C.
A1  - Bergheim, Ina
T1  - Female mice are more susceptible to nonalcoholic fatty liver disease  sex-specific regulation of the hepatic AMP-Activated protein Kinase-Plasminogen activator inhibitor 1 cascade, but not the hepatic endotoxin response
JF  - Molecular medicine
N2  - As significant differences between sexes were found in the susceptibility to alcoholic liver disease in human and animal models, it was the aim of the present study to investigate whether female mice also are more susceptible to the development of nonalcoholic fatty liver disease (NAFLD). Male and female C57BL/6J mice were fed either water or 30% fructose solution ad libitum for 16 wks. Liver damage was evaluated by histological scoring. Portal endotoxin levels and markers of Kupffer cell activation and insulin resistance, plasminogen activator inhibitor 1 (PAI-1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) were measured in the liver. Adiponectin mRNA expression was determined in adipose tissue. Hepatic steatosis was almost similar between male and female mice; however, inflammation was markedly more pronounced in livers of female mice. Portal endotoxin levels, hepatic levels of myeloid differentiation primary response gene (88) (MyD88) protein and of 4-hydroxynonenal protein adducts were elevated in animals with NAFLD regardless of sex. Expression of insulin receptor substrate 1 and 2 was decreased to a similar extent in livers of male and female mice with NAFLD. The less pronounced susceptibility to liver damage in male mice was associated with a superinduction of hepatic pAMPK in these mice whereas, in livers of female mice with NAFLD, PAI-1 was markedly induced. Expression of adiponectin in visceral fat was significantly lower in female mice with NAFLD but unchanged in male mice compared with respective controls. In conclusion, our data suggest that the sex-specific differences in the susceptibility to NAFLD are associated with differences in the regulation of the adiponectin-AMPK-PAI-1 signaling cascade. Online address: http://www.molmed.Org doi: 10.2119/molmed.2012.00223
Y1  - 2012
U6  - https://doi.org/10.2119/molmed.2012.00223
SN  - 1076-1551
VL  - 18
IS  - 9
SP  - 1346
EP  - 1355
PB  - Feinstein Inst. for Medical Research
CY  - Manhasset
ER  -