Long-chain metabolites of vitamin E: Interference with lipotoxicity via lipid droplet associated protein PLIN2 |
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Authors: | Lisa Schmölz Martin Schubert Jasmin Kirschner Stefan Kluge Francesco Galli Marc Birringer Maria Wallert Stefan Lorkowski |
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Institution: | 1. Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Germany;2. Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany;3. Department of Pharmaceutical Sciences, Laboratory of Nutrition and Clinical Biochemistry, University of Perugia, Perugia, Italy;4. Department of Nutritional, Food and Consumer Sciences, University of Applied Sciences Fulda, Germany;5. Baker Heart and Diabetes Institute, Melbourne, Australia |
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Abstract: | The long-chain metabolites of vitamin E (LCM) emerge as a new class of regulatory metabolites and have been considered as the active compounds formed during vitamin E metabolism. The bioactivity of the LCM is comparable to the already established role of other fat-soluble vitamins. The biological modes of action of the LCM are far from being unraveled, but first insights pointed to distinct effects and suggested a specific receptor, which in turn lead to the aforementioned hypothesis. Here, a new facet on the interaction of LCM with foam cell formation of THP-1 macrophages is presented. We found reduced levels of mRNA and protein expression of lipid droplet associated protein PLIN2 by α-tocopherol (α-TOH), whereas the LCM and the saturated fatty acid, stearic acid, increased expression levels of PLIN2. In a lipotoxic setup (0–800?μM stearic acid and 0–100?μM α-TOH or 0–5?μM α-13′-COOH) differences in cellular viability were found. A reduced viability was observed for cells under co-treatment of α-TOH and stearic acid, whereas an increased viability for stearic acid incubation in combination with α-13′-COOH was observed. The striking similarity of PLIN2 expression levels and worsened or mitigated lipotoxicity, respectively, revealed a protective effect of PLIN2 on basal stearic acid-induced lipotoxic conditions in PLIN2 knockdown experiments. Based on our results, we conclude that α-13′-COOH protects cells from lipotoxicity, at least partially via PLIN2 regulation.Herewith another facet of LCM functionality was presented and their reputation as regulatory metabolites was further established. |
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Keywords: | α-13′-OH α-13′-hydroxychromanol α-13′-COOH α-13′-carboxychromanol LCM long-chain metabolites of vitamin E TOH tocopherol T3 tocotrienols Vitamin E Long-chain metabolites of vitamin E α-13′-Hydroxychromanol α-13′-OH α-13′-Carboxychromanol α-13′-COOH |
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