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  • Long-chain metabolites of vitamin E: Interference with lipotoxicity via lipid droplet associated protein PLIN2.

Long-chain metabolites of vitamin E: Interference with lipotoxicity via lipid droplet associated protein PLIN2.

Biochimica et biophysica acta (2018-05-08)
Lisa Schmölz, Martin Schubert, Jasmin Kirschner, Stefan Kluge, Francesco Galli, Marc Birringer, Maria Wallert, Stefan Lorkowski
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human PLIN2
Sigma-Aldrich
MISSION® esiRNA, targeting human UBE2K