TY  - JOUR
A1  - Henkel, Janin
A1  - Coleman, Charles Dominic
A1  - Schraplau, Anne
A1  - Jöhrens, Korinna
A1  - Weber, Daniela
A1  - Castro, Jose Pedro
A1  - Hugo, Martin
A1  - Schulz, Tim Julius
A1  - Krämer, Stephanie
A1  - Schürmann, Annette
A1  - Püschel, Gerhard Paul
T1  - Induction of Steatohepatitis (NASH) with Insulin Resistance in Wild-type B6 Mice by a Western-type Diet Containing Soybean Oil and Cholesterol
JF  - Molecular medicine
N2  - 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.
KW  - Nonalcoholic Steatohepatitis (NASH)
KW  - Typical Western Diet
KW  - Nonalcoholic Fatty Liver Disease (NAFLD)
KW  - Dietary Cholesterol
KW  - Kupffer Cells
Y1  - 2017
U6  - https://doi.org/10.2119/molmed.2016.00203
SN  - 1076-1551
SN  - 1528-3658
VL  - 23
SP  - 70
EP  - 82
PB  - Feinstein Inst. for Medical Research
CY  - Manhasset
ER  - 
TY  - JOUR
A1  - Schulz, Tim Julius
A1  - Thierbach, Renè
A1  - Voigt, Anja
A1  - Drewes, Gunnar
A1  - Mietzner, Brun
A1  - Steinberg, Pablo
A1  - Pfeiffer, Andreas F. H.
A1  - Ristow, Michael
T1  - Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth : Otto Warburg revisited
N2  - More than 80 years ago Otto Warburg suggested that cancer might be caused by a decrease in mitochondrial energy metabolism paralleled by an increase in glycolytic flux. In later years, it was shown that cancer cells exhibit multiple alterations in mitochondrial content, structure, function, and activity. We have stably overexpressed the Friedreich ataxia-associated protein frataxin in several colon cancer cell lines. These cells have increased oxidative metabolism, as shown by concurrent increases in aconitase activity, mitochondrial membrane potential, cellular respiration, and ATP content. Consistent with Warburg's hypothesis, we found that frataxin-overexpressing cells also have decreased growth rates and increased population doubling times, show inhibited colony formation capacity in soft agar assays, and exhibit a reduced capacity for tumor formation when injected into nude mice. Furthermore, overexpression of frataxin leads to an increased phosphorylation of the tumor suppressor p38 mitogen-activated protein kinase, as well as decreased phosphorylation of extracellular signal-regulated kinase. Taken together, these results support the view that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals
Y1  - 2006
UR  - http://www.jbc.org/content/281/2/977.full.pdf+html
U6  - https://doi.org/10.1074/jbc.M511064200
ER  -