Comparison of the effects of dietary stigmasterol and oxidised stigmasterol on fatty acid metabolism in mice fed cholesterol

Abstract Dietary phytosterols exhibit hypocholesterolaemic effects, whereas oxidised phytosterols exert a range of harmful effects. The precise impact of individual oxidised phytosterols, particularly on fatty acid metabolism, remains unclear. Therefore, we compared the effects of dietary stigmasterol and oxidised stigmasterol on fatty acid metabolism in mice. Mice were fed one of the following four diets: a standard American Institute of Nutrition diet, a standard diet plus 0·25 % cholesterol, a standard diet plus 0·25 % cholesterol and 0·25 % stigmasterol or 0·25 % oxidised stigmasterol. Unlike stigmasterol, dietary oxidised stigmasterol increased TAG levels and gene expression levels of sterol regulatory element-binding protein 1c and its downstream enzymes, suggesting that oxidised stigmasterol may stimulate fatty acid synthesis in the liver. Conversely, dietary oxidised stigmasterol increased the gene expression level of PPAR α and its downstream enzymes, either as a compensatory response or as a direct agonist-like activity on PPRA α , and promoted fatty acid synthesis rather than fatty acid β -oxidation. However, dietary oxidised stigmasterol decreased the total fatty acid levels in faeces. Unlike stigmasterol, oxidised stigmasterol increased fatty acid levels in micellar solutions in vitro . Therefore, oxidised stigmasterol may have increased hepatic fatty acid synthesis and enhanced fatty acid absorption from the small intestine, resulting in elevated TAG level in the liver. Consequently, oxidised stigmasterol affects fatty acid metabolism and absorption via a mechanism distinct from that of stigmasterol. These findings raise potential concerns regarding the consumption of foods and supplements containing phytosterols, as oxidation may produce harmful effects on lipid metabolism.