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Intake of stigmasterol and ?-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet.

ABSTRACT: OBJECTIVE:To investigate and compare the effects of two common dietary phytosterols, stigmasterol and ?-sitosterol, in altering lipid metabolism and attenuating nonalcoholic fatty liver disease (NAFLD). METHODS:Stigmasterol and ?-sitosterol were administered to mice at 0.4% in a high-fat western-style diet (HFWD) for 17?weeks. RESULTS:Stigmasterol and ?-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. ?-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 ?-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 ?-sitosterol, possibly because of its suppression of hepatic lipogenic gene expression and modulation of circulating ceramide levels.

SUBMITTER: Feng S

PROVIDER: S-EPMC6226309 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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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.

Feng Simin S Dai Zhuqing Z Liu Anna B AB Huang Jinbao J Narsipur Nihal N Guo Grace G Kong Bo B Reuhl Kenneth K Lu Wenyun W Luo Zisheng Z Yang Chung S CS

Biochimica et biophysica acta. Molecular and cell biology of lipids 20180807 10

<h4>Objective</h4>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).<h4>Methods</h4>Stigmasterol and β-sitosterol were administered to mice at 0.4% in a high-fat western-style diet (HFWD) for 17 weeks.<h4>Results</h4>Stigmasterol and β-sitosterol significantly ameliorated HFWD-induced fatty liver and metabolic abnormalities, including elevated levels of he ...[more]

PMID: 30305244

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Project description:BackgroundConsumption of watermelon has been associated with beneficial effects on metabolism, including reductions in systolic blood pressure, improved fasting blood glucose levels, and changes in hepatic metabolite accumulation.ObjectivesIn the present study, we investigated the impact of consumption of watermelon flesh (WF), watermelon rind (WR), and watermelon skin (WS) on hepatic gene expression patterns in an obesogenic mouse model.MethodsHepatic RNA was isolated and RNA sequencing was performed following a 10-week feeding trial during which C57BL/6 J mice were provided either a low-fat diet (LF), high-fat diet (HF; controls), or HF plus either WS, WR, or WF. Bioinformatic approaches were used to determine changes in the canonical pathways and gene expression levels for lipid- and xenobiotic-regulating nuclear hormone receptors and other related transcription factors, including the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), farnesyl X receptor, peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma, liver X receptor, pregnane X receptor, and nuclear factor erythroid 2-related factor 2.ResultsThere were 9394 genes that had unchanged expression levels between all 5 diet groups, and 247, 58, and 34 genes were uniquely expressed in the WF, WR, and WS groups, respectively. The relative levels of mRNAs regulated by AhR, CAR, and PPARα were upregulated in mice in the WF group, as compared to the HF control mice; in comparison, mRNAs regulated mainly by CAR were upregulated in mice in the WR and WS groups, compared to those in the HF control group.ConclusionsAt modest levels of intake reflective of typical human consumption, mice in the WF, WS, and WR groups exhibited hepatic gene expression profiles that were altered when compared to mice in the HF control group. Several of these changes involve genes regulated by ligand-responsive transcription factors implicated in xenobiotic and lipid metabolisms, suggesting that the modulation of these transcription factors occurred in response to the consumption of WS, WR, and WF. Some of these changes are likely due to nuclear hormone receptor-mediated changes involved in lipid and xenobiotic metabolisms.

Project description:ObjectiveTo identify novel transcriptomic changes to eutopic endometrium by exposure to chronic mild hypernadrogenemia (testosterone [T]) with/without exposure to an obesogenic Western-style diet (WSD).DesignTwo-by-two factorial arrangement of treatments.SettingNational primate research center.AnimalsRhesus macaque females were chronically exposed to T and/or consumed a WSD from menarche through adulthood. After 4.5 years of treatment, Tru-Cut endometrial biopsies were obtained at the midsecretory phase (n = 6-4/group), and paired-end sequencing of RNA was performed. Several females in the T, WSD, and T+WSD cohorts developed endometriosis within 6 months of biopsy; a separate analysis was performed contrasting diagnosis of endometriosis stage 0-2 versus stages 3 and 4 (American Society for Reproductive Medicine revised criteria).InterventionsChronic exposure to mild elevation of T (~five-fold elevation) and/or WSD from menarche until adulthood.Main outcome measuresLimma voom empirical Bayes pipeline was performed to detect differentially expressed RNAs (DEs) significantly impacted by treatments and endometriosis severity. Differentially expressed RNAs were then interrogated by Ingenuity Pathway Analyses and Protein Analysis through Evolutionary Relationships.ResultsTotal DEs included C versus T, 469; C versus WSD, 525; C versus T+WSD, 549; and T versus T+WSD, 1,505. The majority of DEs mapped to the ontology pathways: heterotrimeric G-protein signaling pathways Gi alpha and Gs alpha (C vs. T), WNT signaling (C vs. WSD and T vs. T+WSD), and Huntington disease (C vs. T+WSD). A total of 2,171 DEs from eutopic endometrium were altered by the presence of stage 3 and 4 endometriosis lesions.ConclusionsThe present global transcriptomic analyses demonstrate that the greatest magnitude of changes occurred in contrasts of C and T versus T+WSD, adding to the evidence that these two insults have a synergistic effect on female physiology. These data also support the concept that prior alterations to the function of eutopic endometrium increase the risk for endometriosis.

Dataset Information

Intake of stigmasterol and ?-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet.

Publications

Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet.

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