Suppression of Lipid Accumulation in 3T3-L1 Adipocytes by α-Tocopheryl Succinate.

Obesity is a pathological state related to various lifestyle-related diseases, such as diabetes and dyslipidemia, that may be prevented through the development of anti-obesity treatments. Lipid accumulation in cells could be affected by vitamin E ester α-tocopheryl succinate (TS), which has various biological activities, such as anti-cancer effect, via activation of cell signaling pathways, although the antioxidative activity of TS is lost due to esterification of the phenolic OH group. In this study, we found for the first time that TS significantly suppressed lipid accumulation in mouse 3T3-L1 adipocytes. TS treatment reduced the amount of triglycerides in the culture medium, and inhibited activity of glycerol-3-phosphate dehydrogenase, a marker of lipid synthesis. Furthermore, TS accelerated lipolysis. Treatment of adipocytes with TS for 24 h induced no significant cytotoxicity. In TS-treated cells, phosphorylation of Akt, which is involved in fatty acid synthesis via sterol regulatory element-binding proteins (SREBP), was prevented, while levels of phosphorylated protein kinase A (PKA) did not change. Taken together, these results suggest that vitamin E ester TS can suppress lipid accumulation in adipocytes by regulating lipid metabolic cell signaling.

Isolation of glycosylinositol phosphoceramide and phytoceramide 1-phosphate in plants and their chemical stabilities.

Glycosylinositol phosphoceramide (GIPC) is a sphingophospholipid in plants. Recently, we identified that GIPC is hydrolyzed to phytoceramide 1-phosphate (PC1P) by an uncharacterized phospholipase D activity following homogenization of certain plant tissues. We now developed methods for isolation of GIPC and PC1P from plant tissues and characterized their chemical stabilities. Hydrophilic solvents, namely a lower layer of a mixed solvent system consisting of isopropanol/hexane/water (55:20:25, v/v/v) was efficient solvent for extraction and eluent in column chromatography. GIPC was isolated by Sephadex column chromatography followed by TLC. A conventional method, such as the Bligh and Dyer method, was applicable for PC1P extraction. Specifically, PC1P was isolated by TLC following mild alkali treatment of lipid extracts of plants. The yields of GIPC and PC1P in our methods were both around 50-70%. We found that PC1P is tolerant against heat (up to 125 °C), strong acid (up to 10 M HCl), and mild alkali (0.1 M KOH). In contrast, significant degradation of GIPC occurred at 100 °C and 1.0 M HCl treatment, suggesting the instability of the inositol glycan moiety in these conditions. These data will be useful for further biochemical and nutritional studies on these sphingolipids.

Biological Functions of α-Tocopheryl Succinate.

α-Tocopheryl succinate (TS) is a succinic acid ester of a well-known natural antioxidant α-tocopherol (α-T). Physicochemical characteristics of TS are entirely different from the original compound α-T. TS becomes vesicles via forming a lamella structure. Furthermore, although the antioxidative activity of α-T is lacked by esterification of phenolic hydroxyl (OH) moiety with succinate, TS has versatile biological functions, such as inhibition of cholinesterase activity, inhibition of nuclear factor-kappa B (NF-κB) activation, enhancement of lipopolysaccharide-induced nitric oxide production, and anticancer effect. Especially, we expect TS as a novel anticancer agent. TS nanovesicle shows significant anticancer activity in vitro and in vivo. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide which mediates the anticancer activity of TS. Moreover, it suggests that TS activates protein kinase C via direct interaction. Based on the analysis of structure and activity relationship, it ensures that succinate moiety of TS plays a vital role in anticancer activity. This review introduces the detail and mechanism of versatile biological functions of TS.