@article{SprussHenkelKanurietal.2012,
  author    = {Spruss, Astrid and Henkel, Janin and Kanuri, Giridhar and Blank, Daniela and P{\"u}schel, Gerhard Paul and Bischoff, Stephan C. and Bergheim, Ina},
  title     = {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},
  series = {Molecular medicine},
  volume    = {18},
  journal   = {Molecular medicine},
  number    = {9},
  publisher = {Feinstein Inst. for Medical Research},
  address   = {Manhasset},
  issn      = {1076-1551},
  doi       = {10.2119/molmed.2012.00223},
  pages     = {1346 -- 1355},
  year      = {2012},
  abstract  = {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},
  language  = {en}
}
@article{HenkelColemanSchraplauetal.2017,
  author    = {Henkel, Janin and Coleman, Charles Dominic and Schraplau, Anne and J{\"o}hrens, Korinna and Weber, Daniela and Castro, Jose Pedro and Hugo, Martin and Schulz, Tim Julius and Kr{\"a}mer, Stephanie and Sch{\"u}rmann, Annette and P{\"u}schel, Gerhard Paul},
  title     = {Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol},
  series = {Molecular medicine},
  volume    = {23},
  journal   = {Molecular medicine},
  publisher = {Feinstein Inst. for Medical Research},
  address   = {Manhasset},
  issn      = {1076-1551},
  doi       = {10.2119/molmed.2016.00203},
  pages     = {70 -- 82},
  year      = {2017},
  abstract  = {Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g., high-fat diets) or overweight and insulin resistance (e.g., methionine-choline-deficient diets), or they are based on monogenetic defects (e.g., ob/ob mice). In the current study, a Western-type diet containing soybean oil with high n-6-PUFA and 0.75\% cholesterol (SOD + Cho) induced steatosis, inflammation and fibrosis accompanied by hepatic lipid peroxidation and oxidative stress in livers of C57BL/6-mice, which in addition showed increased weight gain and insulin resistance, thus displaying a phenotype closely resembling all clinical features of NASH in patients with metabolic syndrome. In striking contrast, a soybean oil-containing Western-type diet without cholesterol (SOD) induced only mild steatosis but not hepatic inflammation, fibrosis, weight gain or insulin resistance. Another high-fat diet, mainly consisting of lard and supplemented with fructose in drinking water (LAD + Fru), resulted in more prominent weight gain, insulin resistance and hepatic steatosis than SOD + Cho, but livers were devoid of inflammation and fibrosis. Although both LAD + Fru-and SOD + Cho-fed animals had high plasma cholesterol, liver cholesterol was elevated only in SOD + Cho animals. Cholesterol induced expression of chemotactic and inflammatory cytokines in cultured Kupffer cells and rendered hepatocytes more susceptible to apoptosis. In summary, dietary cholesterol in the SOD + Cho diet may trigger hepatic inflammation and fibrosis. SOD + Cho-fed animals may be a useful disease model displaying many clinical features of patients with the metabolic syndrome and NASH.},
  language  = {en}
}