TY  - JOUR
A1  - Henkel, Janin
A1  - Alfine, Eugenia
A1  - Saín, Juliana
A1  - Jöhrens, Korinna
A1  - Weber, Daniela
A1  - Castro, José Pedro
A1  - König, Jeannette
A1  - Stuhlmann, Christin
A1  - Vahrenbrink, Madita
A1  - Jonas, Wenke
A1  - Kleinridders, André
A1  - Püschel, Gerhard Paul
T1  - Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol
JF  - Nutrients
N2  - While the impact of dietary cholesterol on the progression of atherosclerosis has probably been overestimated, increasing evidence suggests that dietary cholesterol might favor the transition from blunt steatosis to non-alcoholic steatohepatitis (NASH), especially in combination with high fat diets. It is poorly understood how cholesterol alone or in combination with other dietary lipid components contributes to the development of lipotoxicity. The current study demonstrated that liver damage caused by dietary cholesterol in mice was strongly enhanced by a high fat diet containing soybean oil-derived ω6-poly-unsaturated fatty acids (ω6-PUFA), but not by a lard-based high fat diet containing mainly saturated fatty acids. In contrast to the lard-based diet the soybean oil-based diet augmented cholesterol accumulation in hepatocytes, presumably by impairing cholesterol-eliminating pathways. The soybean oil-based diet enhanced cholesterol-induced mitochondrial damage and amplified the ensuing oxidative stress, probably by peroxidation of poly-unsaturated fatty acids. This resulted in hepatocyte death, recruitment of inflammatory cells, and fibrosis, and caused a transition from steatosis to NASH, doubling the NASH activity score. Thus, the recommendation to reduce cholesterol intake, in particular in diets rich in ω6-PUFA, although not necessary to reduce the risk of atherosclerosis, might be sensible for patients suffering from non-alcoholic fatty liver disease.
KW  - non-alcoholic fatty liver disease (NAFLD)
KW  - NASH
KW  - cholesterol
KW  - PUFA
KW  - inflammation
KW  - oxidative stress
Y1  - 2018
U6  - https://doi.org/10.3390/nu10091326
SN  - 2072-6643
VL  - 10
IS  - 9
SP  - 1
EP  - 17
PB  - Molecular Diversity Preservation International (MDPI)
CY  - Basel
ER  - 
TY  - JOUR
A1  - Kobel-Höller, Konstanze
A1  - Gley, Kevin
A1  - Jochinke, Janina
A1  - Heider, Kristina
A1  - Fritsch, Verena Nadin
A1  - Ha Viet Duc Nguyen, 
A1  - Lischke, Timo
A1  - Radek, Renate
A1  - Baumgrass, Ria
A1  - Mutzel, Rupert
A1  - Thewes, Sascha
T1  - Calcineurin Silencing in Dictyostelium discoideum Leads to Cellular Alterations Affecting Mitochondria, Gene Expression, and Oxidative Stress Response
JF  - Protist
N2  - Calcineurin is involved in development and cell differentiation of the social amoeba Dictyostelium discoideum. However, since knockouts of the calcineurin-encoding genes are not possible in D. discoideum it is assumed that the phosphatase also plays a crucial role during vegetative growth of the amoebae. Therefore, we investigated the role of calcineurin during vegetative growth in D. discoideum. RNAi-silenced calcineurin mutants showed cellular alterations with an abnormal morphology of mitochondria and had increased content of mitochondrial DNA (mtDNA). In contrast, mitochondria showed no substantial functional impairment. Calcineurin-silencing led to altered expression of calcium-regulated genes as well as mitochondrially-encoded genes. Furthermore, genes related to oxidative stress were higher expressed in the mutants, which correlated to an increased resistance towards reactive oxygen species (ROS). Most of the changes observed during vegetative growth were not seen after starvation of the calcineurin mutants. We show that impairment of calcineurin led to many subtle, but in the sum crucial cellular alterations in vegetative D. discoideum cells. As these alterations were not observed after starvation we propose a dual role for calcineurin during growth and development. Our results imply that calcineurin is one player in the mutual interplay between mitochondria and ROS during vegetative growth.
KW  - mtDNA
KW  - mitochondrial remodelling
KW  - calcium
KW  - oxidative stress
KW  - phototaxis
Y1  - 2018
U6  - https://doi.org/10.1016/j.protis.2018.04.004
SN  - 1434-4610
VL  - 169
IS  - 4
SP  - 584
EP  - 602
PB  - Elsevier GMBH
CY  - München
ER  -