Oxysterols: From cholesterol metabolites to key mediators

Mutemberezi, Valentin; Guillemot-Legris, Owein; Muccioli, Giulio G.

doi:10.1016/j.plipres.2016.09.002

Cited by 263 publications

(229 citation statements)

References 210 publications

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“…The assay method may be the source of variations in oxysterols between the studies, e.g., the observed median of 27-hydroxycholesterol was between 55.6–58.7 ng/ml in the previous study and 27.9–31.7 in the present one. On the other hand, the mean levels of the rest of oxysterols we analyzed are comparable to other published data in humans (Mutemberezi 2016). …”

Section: Discussionsupporting

confidence: 89%

“…Griffiths 2016 for review) and thus their role in breast cancer is currently attracting considerable interest. Although human plasma levels of oxysterols have already been assessed by various authors (reviewed, e.g., in Mutemberezi 2016), there is currently only one very recent study reporting differences in levels of various oxysterols in plasma of breast cancer patients (Dalenc 2016). Thus, our study adds novel information essential for this evolving area of research.…”

Section: Discussionmentioning

confidence: 99%

“…Oxygenated metabolites of cholesterol belong to a large group of sterols called oxysterols (Mutemberezi 2016). Oxysterols are formed in the human body or ingested in the diet, e.g., phytosterols.…”

Section: Introductionmentioning

confidence: 99%

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Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Souček

Vrána

Ueng

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Introduction Oxygenated metabolites of cholesterol (“oxysterols”) can influence carcinogenesis and contribute to resistance to endocrine therapy, an effect mostly described in vitro. Objectives We sought to establish a method for screening plasma levels of oxysterols in breast cancer patients, estimate their individual variability and detection limits, and provide basic information about their roles in tumor biology. Method Liquid-chromatography coupled with tandem mass spectrometry was used for determination of levels of 25-hydroxycholesterol, 27-hydroxycholesterol, 7α-hydroxycholesterol, and 7-ketocholesterol in plasma sample pairs from patients before and 12–24 months after surgical removal of tumors (n=24). Deuterated standards of all oxysterols were used for method validation. Result All oxysterols were successfully detected in patient plasma samples. A significant increase in the level of 7-ketocholesterol was observed in the samples following tumor removal and the start of therapy compared to the sampling before (p=0.002). This increase was unrelated to personal characteristics of patients, expression of estrogen receptor, or to adjuvant therapy type. Conclusion This study shows, for the first time, that circulating levels of oxysterols, especially 7-ketocholesterol, may reflect the presence of tumor cells in patients.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Souček

Vrána

Ueng

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Cholesterol is an indispensable building block for all cell membranes and is incorporated in considerable amounts into myelin in the nervous system during the period of rapid brain growth, and it serves as the substrate for the synthesis of bile acids, lipoproteins, vitamin D, hormones, and oxysterols that modulate cholesterol, lipid, and glucose homeostasis [3,9,[17][18][19] . The provision of cholesterol with breastfeeding is associated with higher plasma concentrations of total and low-density lipoprotein cholesterol in breastfed than in formula-fed infants [20] .…”

Section: Cholesterolmentioning

confidence: 99%

Human Milk Lipids

2016

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Human milk lipids provide the infant with energy and essential vitamins, polyunsaturated fatty acids, and bioactive components. Adding complex lipids and milk fat globule membranes to vegetable oil-based infant formula has the potential to enhance infant development and reduce infections. Cholesterol provision with breastfeeding modulates infant sterol metabolism and may induce long-term benefits. Some 98-99% of milk lipids are comprised by triacylglycerols, whose properties depend on incorporated fatty acids. Attention has been devoted to the roles of the long-chain polyunsaturated fatty acids docosahexaenoic (DHA) and arachidonic (ARA) acids. Recent studies on gene-diet interaction (Mendelian randomization) show that breastfeeding providing DHA and ARA improves cognitive development and reduces asthma risk at school age particularly in those children with a genetically determined lower activity of DHA and ARA synthesis. It appears prudent to follow the biological model of human milk in the design of infant formula as far as feasible, unless conclusive evidence for the suitability and safety of other choices is available. The recent European Union legislative stipulation of a high formula DHA content without required ARA deviates from this concept, and such a novel formula composition has not been adequately evaluated. Great future opportunities arise with significant methodological progress for example in lipidomic analyses and their bioinformatic evaluation, which should enhance understanding of the biology of human milk lipids. Such knowledge might lead to improved dietary advice to lactating mothers as well as to further opportunities to enhance infant formula composition.

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“…Several oxysterols, such 24-, 25- and 27-hydroxycholesterol, can serve as endogenous LXRα agonists [20]. We determined that expression of CYP46A1, CH25H and CYP27A1, the enzymes are responsive for production of 24-, 25- and 27-hydrocholesterol, respectively, in HepG2 cells was reduced by atorvastatin (Fig.…”

Section: Resultsmentioning

confidence: 99%

Activation of hepatic Nogo-B receptor expression—A new anti-liver steatosis mechanism of statins

Zhang

Yang

Chen

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum. In vitro, statins reduced lipid accumulation in nonsilencing small hairpin RNA-transfected Conflict of interestNone declared. Transparency documentThe http://dx.doi.org/10.1016/j.bbalip.2017.12.002 associated with this article can be found, in online version. HHS Public Access

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Oxysterols: From cholesterol metabolites to key mediators

Cited by 263 publications

References 210 publications

Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Selective changes in cholesterol metabolite levels in plasma of breast cancer patients after tumor removal

Human Milk Lipids

Activation of hepatic Nogo-B receptor expression—A new anti-liver steatosis mechanism of statins

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