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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

Title data

Spruss, Astrid ; Henkel, Janin ; Kanuri, Giridhar ; Blank, Daniela ; Püschel, Gerhard P. ; Bischoff, Stephan C. ; Bergheim, Ina:
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.
In: Molecular Medicine. Vol. 18 (6 December 2012) Issue 1 . - pp. 1346-1355.
ISSN 1528-3658
DOI: https://doi.org/10.2119/molmed.2012.00223

Abstract in another language

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 non-alcoholic 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.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Life Sciences: Food, Nutrition and Health
Faculties
Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung > Lehrstuhl Biochemie der Ernährung - Univ.-Prof. Dr. Janin Henkel-Oberländer
Faculties > Faculty of Life Sciences: Food, Nutrition and Health > Lehrstuhl Biochemie der Ernährung
Result of work at the UBT: No
DDC Subjects: 500 Science > 500 Natural sciences
500 Science > 570 Life sciences, biology
Date Deposited: 26 Apr 2021 11:33
Last Modified: 17 May 2021 06:53
URI: https://eref.uni-bayreuth.de/id/eprint/64432