- 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 resultedOverconsumption 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.…
MetadatenAuthor details: | Mareike SchellORCiDGND, Chantal Chudoba, Antoine LeboucherORCiD, Eugenia Alfine, Tanina Flore, Katrin Ritter, Katharina Weiper, Andreas Wernitz, Janin HenkelORCiDGND, André KleinriddersORCiDGND |
---|
URN: | urn:nbn:de:kobv:517-opus4-470773 |
---|
DOI: | https://doi.org/10.25932/publishup-47077 |
---|
ISSN: | 1866-8372 |
---|
Title of parent work (German): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
---|
Publication series (Volume number): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (946) |
---|
Publication type: | Postprint |
---|
Language: | English |
---|
Date of first publication: | 2020/06/05 |
---|
Publication year: | 2020 |
---|
Publishing institution: | Universität Potsdam |
---|
Release date: | 2020/06/05 |
---|
Tag: | JNK; brain; cholesterol; fatty acids; inflammation; insulin receptor; insulin signaling; mitochondria |
---|
Issue: | 946 |
---|
Number of pages: | 24 |
---|
Source: | Nutrients 12 (2020) 5, 1518 DOI: 10.3390/nu12051518 |
---|
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät |
---|
DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
---|
Peer review: | Referiert |
---|
Publishing method: | Open Access |
---|
License (German): | CC-BY - Namensnennung 4.0 International |
---|
External remark: | Bibliographieeintrag der Originalveröffentlichung/Quelle |
---|