The vitamin E long-chain metabolite α-13′-COOH affects macrophage foam cell formation via modulation of the lipoprotein lipase system

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids 2021-04, Vol.1866 (4), p.158875-158875, Article 158875
• Main Authors: Kluge, Stefan, Schubert, Martin, Börmel, Lisa, Lorkowski, Stefan
• Format: Article
• Language: English
• Subjects: ANGPTL4; Foam cell formation; Lipoprotein lipase; Vitamin E; α-13′-COOH; α-Tocopherol
• ISSN: 1388-1981; 1879-2618
• DOI: 10.1016/j.bbalip.2021.158875

The α-tocopherol-derived long-chain metabolite (α-LCM) α-13′-carboxychromanol (α-13′-COOH) is formed via enzymatic degradation of α-tocopherol (α-TOH) in the liver. In the last decade, α-13′-COOH has emerged as a new regulatory metabolite revealing more potent or even different effects compared with its vitamin precursor α-TOH. The detection of α-13′-COOH in human serum has further strengthened the concept of its physiological relevance as a potential regulatory molecule. Here, we present a new facet on the interaction of α-13′-COOH with macrophage foam cell formation. We found that α-13′-COOH (5 μM) increases angiopoietin-like 4 (ANGPTL4) mRNA expression in human THP-1 macrophages in a time- and dose-dependent manner, while α-TOH (100 μM) showed no effects. Interestingly, the mRNA level of lipoprotein lipase (LPL) was not influenced by α-13′-COOH, but α-TOH treatment led to a reduction of LPL mRNA expression. Both compounds also revealed different effects on protein level: while α-13′-COOH reduced the secreted amount of LPL protein via induction of ANGPTL4 cleavage, i.e. activation, the secreted amount of LPL in the α-TOH-treated samples was diminished due to the inhibition of mRNA expression. In line with this, both compounds reduced the catalytic activity of LPL. However, α-13′-COOH but not α-TOH attenuated VLDL-induced lipid accumulation by 35%. In conclusion, only α-13′-COOH revealed possible antiatherogenic effects due to the reduction of VLDL-induced foam cell formation in THP-1 macrophages. Our results provide further evidence for the role of α-13′-COOH as a functional metabolite of its vitamin E precursor. [Display omitted] •α-13′-COOH induces ANGPTL4 mRNA expression and ANGPTL4 processing.•α-13′-COOH reduces the secreted amount of LPL protein.•α-TOH and α-13′-COOH inhibit VLDL induced catalytic activity of LPL in human THP-1 macrophages.•α-13′-COOH attenuates VLDL induced foam cell formation in human THP-1 macrophages.•α-13′-COOH acts via a hitherto unknown regulatory mechanism different from its vitamin precursor α-TOH.