TY  - JOUR
A1  - Schell, Mareike
A1  - Chudoba, Chantal
A1  - Leboucher, Antoine
A1  - Alfine, Eugenia
A1  - Flore, Tanina
A1  - Ritter, Katrin
A1  - Weiper, Katharina
A1  - Wernitz, Andreas
A1  - Henkel, Janin
A1  - Kleinridders, André
T1  - Interplay of Dietary Fatty Acids and Cholesterol Impacts Brain Mitochondria and Insulin Action
JF  - Nutrients
N2  - Overconsumption of high-fat and cholesterol-containing diets is detrimental for metabolism and mitochondrial function, causes inflammatory responses and impairs insulin action in peripheral tissues. Dietary fatty acids can enter the brain to mediate the nutritional status, but also to influence neuronal homeostasis. Yet, it is unclear whether cholesterol-containing high-fat diets (HFDs) with different combinations of fatty acids exert metabolic stress and impact mitochondrial function in the brain. To investigate whether cholesterol in combination with different fatty acids impacts neuronal metabolism and mitochondrial function, C57BL/6J mice received different cholesterol-containing diets with either high concentrations of long-chain saturated fatty acids or soybean oil-derived poly-unsaturated fatty acids. In addition, CLU183 neurons were stimulated with combinations of palmitate, linoleic acid and cholesterol to assess their effects on metabolic stress, mitochondrial function and insulin action. The dietary interventions resulted in a molecular signature of metabolic stress in the hypothalamus with decreased expression of occludin and subunits of mitochondrial electron chain complexes, elevated protein carbonylation, as well as c-Jun N-terminal kinase (JNK) activation. Palmitate caused mitochondrial dysfunction, oxidative stress, insulin and insulin-like growth factor-1 (IGF-1) resistance, while cholesterol and linoleic acid did not cause functional alterations. Finally, we defined insulin receptor as a novel negative regulator of metabolically stress-induced JNK activation.
KW  - cholesterol
KW  - insulin signaling
KW  - mitochondria
KW  - brain
KW  - inflammation
KW  - fatty acids
KW  - JNK
KW  - insulin receptor
Y1  - 2020
U6  - https://doi.org/10.3390/nu12051518
SN  - 2072-6643
VL  - 12
IS  - 5
PB  - MDPI
CY  - Basel
ER  - 
TY  - GEN
A1  - Schell, Mareike
A1  - Chudoba, Chantal
A1  - Leboucher, Antoine
A1  - Alfine, Eugenia
A1  - Flore, Tanina
A1  - Ritter, Katrin
A1  - Weiper, Katharina
A1  - Wernitz, Andreas
A1  - Henkel, Janin
A1  - Kleinridders, André
T1  - Interplay of Dietary Fatty Acids and Cholesterol Impacts Brain Mitochondria and Insulin Action
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Overconsumption of high-fat and cholesterol-containing diets is detrimental for metabolism and mitochondrial function, causes inflammatory responses and impairs insulin action in peripheral tissues. Dietary fatty acids can enter the brain to mediate the nutritional status, but also to influence neuronal homeostasis. Yet, it is unclear whether cholesterol-containing high-fat diets (HFDs) with different combinations of fatty acids exert metabolic stress and impact mitochondrial function in the brain. To investigate whether cholesterol in combination with different fatty acids impacts neuronal metabolism and mitochondrial function, C57BL/6J mice received different cholesterol-containing diets with either high concentrations of long-chain saturated fatty acids or soybean oil-derived poly-unsaturated fatty acids. In addition, CLU183 neurons were stimulated with combinations of palmitate, linoleic acid and cholesterol to assess their effects on metabolic stress, mitochondrial function and insulin action. The dietary interventions resulted in a molecular signature of metabolic stress in the hypothalamus with decreased expression of occludin and subunits of mitochondrial electron chain complexes, elevated protein carbonylation, as well as c-Jun N-terminal kinase (JNK) activation. Palmitate caused mitochondrial dysfunction, oxidative stress, insulin and insulin-like growth factor-1 (IGF-1) resistance, while cholesterol and linoleic acid did not cause functional alterations. Finally, we defined insulin receptor as a novel negative regulator of metabolically stress-induced JNK activation.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 946 
KW  - cholesterol
KW  - insulin signaling
KW  - mitochondria
KW  - brain
KW  - inflammation
KW  - fatty acids
KW  - JNK
KW  - insulin receptor
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-470773
SN  - 1866-8372
IS  - 946
ER  -