Objective:
To investigate and compare the effects of two common dietary phytosterols, stigmasterol and β-sitosterol, in altering lipid metabolism and attenuating nonalcoholic fatty liver disease (NAFLD).
Methods:
Stigmasterol and β-sitosterol were administered to mice at 0.4% in a high-fat western-style diet (HFWD) for 17 weeks.
Results:
Stigmasterol and β-sitosterol significantly ameliorated HFWD-induced fatty liver and metabolic abnormalities, including elevated levels of hepatic total lipids, triacylglycerols, cholesterol and liver histopathology. Both phytosterols decreased the levels of intestinal bile acids, accompanied by markedly increased fecal lipid levels. In addition, they altered the expression of genes involved in lipid metabolism. β-Sitosterol was less effective in affecting most of these parameters. Lipidomic analysis of liver and serum samples showed that stigmasterol prevented the HFWD-induced elevation of some di- and triacylglycerol species and lowering of some phospholipid species. Stigmasterol also decreased serum levels of ceramides.
Conclusion:
Stigmasterol and β-sitosterol, at a dose corresponding to that suggested for humans by the FDA for lowering cholesterol levels, are shown to alleviate HFWD-induced NAFLD. Stigmasterol was more effective than β-sitosterol, possibly because of its suppression of hepatic lipogenic gene expression and modulation of circulating ceramide levels.
EGCG decreases bile acid reabsorption, results in lower intestinal bile acid levels, which further decreases the absorption of lipids. These actions contribute to the alleviation of metabolic abnormalities and fatty liver disease caused by the high-fat diet.
To study the effects of stigmasterol and β-sitosterol on high-fat Western diet (HFWD)-induced nonalcoholic fatty liver disease (NAFLD), lipidomic analyses were conducted in liver samples collected after 33 weeks of the treatment. Principal component analysis showed these phytosterols were effective in protecting against HFWD-induced NAFLD. Orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and S-plots showed that triacylglycerols (TGs), phosphatidylcholines, cholesteryl esters, diacylglycerols, and free fatty acids (FFAs) were the major lipid species contributing to these discriminations. The alleviation of NAFLD is mainly associated with decreases in hepatic cholesterol, TGs with polyunsaturated fatty acids, and alterations of free hepatic FFA. In conclusion, phytosterols, at a dose comparable to that suggested for humans by the FDA for the reduction of plasma cholesterol levels, are shown to protect against NAFLD in this long-term (33-week) study.
Phytosterols, the plant analogues of cholesterol, widely occur in the human diet. In this study, we investigated and compared the effects of stigmasterol and β-sitosterol (both with purities ≥ 95%) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J male mice fed a high fat western-style diet. Mice treated with DSS developed severe mucosal colitis, with a marked distortion and crypt loss of colonic surface epithelium. Both β-sitosterol and stigmasterol significantly inhibited colon shortening, lowered fecal hemoglobin contents, and reduced the severity of colitis in the middle and distal colon (p < 0.05). They also significantly suppressed the activation of inflammatory master regulator nuclear factor-kappa B. Stigmasterol significantly lowered colonic inflammation score and the expression of cyclooxygenase-2 and colony stimulating factor-1, while β-sitosterol was less or not effective. These results suggest that dietary intake of stigmasterol and β-sitosterol ameliorate colitis. Such activities of stigmasterol and β-sitosterol in humans remain to be investigated.
Consumption of phytosterols (PSs), the plant‐based analogs of cholesterol, can reduce serum cholesterol levels. This review discusses the current state of the art into the research of the structural features and dietary sources of PSs and their derivatives. The effect of PSs on individual lipid metabolites is summarized in the present review. PS‐related nonalcoholic fatty liver disease (NAFLD), obesity, and the alleviation of inflammatory bowel diseases are discussed. PSs reduce the risk of having NAFLD by improving the blood biochemical parameters related to lipid transport and metabolism. However, current research on the circulating PSs indicates its safety concern regarding fatty liver disease induction. In addition, PS oxidation products exhibit pro‐atherogenic properties, cytotoxicity oxidative stress, apoptosis, and pro‐inflammatory properties. Further research is needed to investigate the bioavailability and safety issues of PSs and their derivatives in animal models and clinical trials.
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