Ximenynic Acid Regulation of n-3 PUFA Content in Liver and Brain

Abstract

Background/Aims: Ximenynic acid is a rare conjugated enyne fatty acid found primarily in plants in the Santalaceae family. It has been reported that sandalwood seed oil (SWSO) affects fatty acid metabolism in animal studies; however, the effects of pure ximenynic acid remain unclear. The present study aimed to study the impact of SWSO and ximenynic acid on n-3 fatty acid metabolism in the liver and brain. Methods: Thirty C57BL/6 male mice aged 4 weeks were fed SWSO (1.0 mL/20 g bodyweight), olive oil (OO), or a combination of SWSO and OO (n = 10/group) for 8 weeks. Liver and brain fatty acid compositions were determined using gas chromatography. HepG2 cells were treated with up to 150 μM ximenynic acid and oleic acid for 48–72 h. The expression and abundance of genes and proteins relevant to n-3 fatty acid metabolism pathways were investigated. Results: The intake of SWSO in mice elevated the levels of total n-3 fatty acids and decreased total n-9 fatty acids in the liver (p < 0.05) compared with the OO group. In contrast, total n-3 fatty acids were significantly decreased in the brain (p < 0.05). HepG2 cells treated with ximenynic acid for 48 h showed significant reductions in n-9 fatty acids and docosahexaenoic acid (C22:6n-3) (p < 0.05) compared with HepG2 cells treated with oleic acid. In HepG2 cells, stearoyl-CoA desaturase (SCD) and fatty acid desaturase 2 (FADS2) gene expression, as well as FADS2 protein expression, were significantly down-regulated after a 72-h incubation with 150 μM of ximenynic acid compared with the vehicle (p < 0.05). Conclusion: Ximenynic acid may regulate fatty acid metabolism by suppressing the expression of key enzymes of lipid metabolism. In contrast, SWSO, which has a high level of C18:3n-3, positively affected n-3 fatty acid synthesis in mouse liver compared to pure ximenynic acid. We hypothesize that a high level of precursor C18:3n-3 in SWSO promotes the endogenous synthesis of C22:6n-3 despite the presence of ximenynic acid.