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Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet
Authors:Simin Feng  Zhuqing Dai  Anna B Liu  Jinbao Huang  Nihal Narsipur  Grace Guo  Bo Kong  Kenneth Reuhl  Wenyun Lu  Zisheng Luo  Chung S Yang
Institution:1. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA;2. Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, People''s Republic of China;3. Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou, 310014, People''s Republic of China;4. College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, People''s Republic of China;5. State Key Laboratory of Tea Plant Biology and Utilization School of Tea & Food Science, Anhui Agricultural University, Hefei, Anhui, People''s Republic of China;6. Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA;7. Department of Chemistry & Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA
Abstract:

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.
Keywords:ABCA1  ATP binding cassette transporter A1  ABCG5  ATP binding cassette transporter 5  ALT  alanine aminotransferase  ASBT  ileal apical sodium-dependent bile acid transporter  BA  bile acid(s)  BSEP  bile salt export pump  CD36  Cluster of Differentiation 36  CM  ceramide(s)  CYP7A1  cholesterol 7α-hydroxylase gene  CYP8B1  sterol 12α-hydroxylase  CYP27A1  sterol 27-hydroxylase  DG  diacylglycerol(s)  FAS  fatty acid synthase  FFA  free fatty acid(s)  FGF15  Fibroblast growth factor 15  FXR  farnesoid x receptor  HDL-C  high-density lipoprotein cholesterol  HFWD  high-fat western-style diet  HMGCoAR  hydroxymethylglutaryl coenzyme A reductase  non-HDL-C  non-high-density lipoprotein cholesterol  LDLr  low density lipoprotein receptor  LFD  low-fat diet  NAFLD  nonalcoholic fatty liver disease  NASH  non-alcoholic steatohepatitis  NTCP  +  OPLS-DA  orthogonal projections to latent structures-disciminate analysis  PE  phosphatidylethanolamine(s)  PC  phosphatidylcholine(s)  PPARα  peroxisome proliferator-activated receptor α  PUFA  polyunsaturated fatty acid(s)  SCD1  stearoyl-CoA desaturas-1  SM  sphingomyelin(s)  SR-B1  scavenger 8n  TG  triacylglycerol(s)  SHP  small heterodimer partner  TBA  total bile acid(s)  Stigmasterol  β-Sitosterol  Fatty liver  Mice  Cholesterol  Lipidomics
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