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

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.