Increased 27-hydroxycholesterol plasma level in men with low high density lipoprotein-cholesterol may circumvent their reduced cell cholesterol efflux rate

Nunes, V.S.; Panzoldo, Natália Baratella; Leança, Camila Canteiro; Parra, Eliane Soler; Zago, Vanessa Helena de Souza; Silva, Eliton J. da; Cazita, P.M.; Nakandakare, Edna Regina; Faria, Eliana Cotta de; Quintão, Eder Carlos Rocha

doi:10.1016/j.cca.2014.03.017

Cited by 16 publications

(13 citation statements)

References 33 publications

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“…Interest in sexually dimorphic drug metabolism and liver disease development lead to several studies describing Cyp27a1 expression and activity differences in adult males and females. Basal levels of Cyp27a1 expression appear to be equal in men and women; however, the concentration of its product, 27-hydroxycholesterol, is lower in females suggesting differences in activity levels [62]. The presence of high cholesterol in the diet causes a downregulation of Cyp27a1 expression in males and females equally [63] (Table 2).…”

Section: Enzymes Of the Classical And Alternative Bile Acid Synthesismentioning

confidence: 99%

The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis

et al. 2019

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Obesity and elevated serum lipids are associated with a threefold increase in the risk of developing atherosclerosis, a condition that underlies stroke, myocardial infarction, and sudden cardiac death. Strategies that aim to reduce serum cholesterol through modulation of liver enzymes have been successful in decreasing the risk of developing atherosclerosis and reducing mortality. Statins, which inhibit cholesterol biosynthesis in the liver, are considered among the most successful compounds developed for the treatment of cardiovascular disease. However, recent debate surrounding their effectiveness and safety prompts consideration of alternative cholesterol-lowering therapies, including increasing cholesterol catabolism through bile acid (BA) synthesis. Targeting the enzymes that convert cholesterol to BAs represents a promising alternative to other cholesterol-lowering approaches that treat atherosclerosis as well as fatty liver diseases and diabetes mellitus. Compounds that modify the activity of these pathways have been developed; however, there remains a lack of consideration of biological sex. This is necessary in light of strong evidence for sexual dimorphisms not only in the incidence and progression of the diseases they influence but also in the expression and activity of the proteins affected and in the manner in which men and women respond to drugs that modify lipid handling in the liver. A thorough understanding of the enzymes involved in cholesterol catabolism and modulation by biological sex is necessary to maximize their therapeutic potential.

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Section: Enzymes Of the Classical And Alternative Bile Acid Synthesismentioning

confidence: 99%

The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis

et al. 2019

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“…We found lower 24-OHC (p = 0.024), and borderline lower 27-OHC (p = 0.07) plasma concentration (ng/mg of cholesterol) in the High HDL group (Table 2) even when expressed by the cholesterol content in each lipoprotein component (Figures 1B,C). Also, significant inversely proportional correlations were shown in HDL between 24-OHC/Cholesterol and 27-OHC/Cholesterol vs. HDL, suggesting that the High HDL plasma group does not provide greater efficiency for cellular export of cholesterol metabolites as previously shown (13).…”

Section: Discussionmentioning

confidence: 57%

The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration

et al. 2022

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Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.

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“…In humans with hypoalphalipoproteinemia increase in plasma concentration of 27-OH C has been reported, which may overlap their reduced cell cholesterol efflux rate (Nunes et al, 2014 ). Independently of genetics and metabolic fate, the HDL cholesterol range in plasma is linked to a 40% variation in 27-OH C associated to HDL particle (Karuna et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Aerobic Exercise Training Selectively Changes Oxysterol Levels and Metabolism Reducing Cholesterol Accumulation in the Aorta of Dyslipidemic Mice

et al. 2017

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Background: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET) prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT) and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration.Methods: Sixteen-week old male apo E KO mice fed a chow diet were included in the protocol. Animals were trained in a treadmill running, 15 m/min, 5 days/week, for 60 min (T; n = 29). A control group was kept sedentary (S; n = 32). Plasma lipids and glucose were determined by enzymatic techniques and glucometer, respectively. Cholesterol and oxysterols in aortic arch and macrophages were measured by gas chromatography/mass spectrometry. The expression of genes involved in lipid metabolism was determined by RT-qPCR. The effect of AMPK in oxysterols metabolism was determined in J774 macrophages treated with 0.25 mM AICAR.Results: Body weight and plasma TC, TG, HDL-c, glucose, and oxysterols were similar between groups. As compared to S group, AET enhanced 7β-hydroxycholesterol (70%) and reduced cholesterol (32%) in aorta. In addition, exercise increased Cyp27a1 (54%), Cd36 (75%), Cat (70%), Prkaa1 (40%), and Prkaa2 (51%) mRNA. In macrophages, the activation of AMPK followed by incubation with HDL2 increased Abca1 (52%) and Cd36 (220%) and decrease Prkaa1 (19%), Cyp27a1 (47%) and 7α-hydroxycholesterol level.Conclusion: AET increases 7β-hydroxycholesterol in the aortic arch of dyslipidemic mice, which is related to the enhanced expression of Cd36. In addition, the increase and reduction of Cyp27a1 and Cyp7b1 in trained mice may contribute to enhance levels of 27-OH C. Both oxysterols may act as an alternative pathway for the RCT contributing to the reduction of cholesterol in the aortic arch preventing atherogenesis.

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Increased 27-hydroxycholesterol plasma level in men with low high density lipoprotein-cholesterol may circumvent their reduced cell cholesterol efflux rate

Cited by 16 publications

References 33 publications

The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis

The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis

The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration

Aerobic Exercise Training Selectively Changes Oxysterol Levels and Metabolism Reducing Cholesterol Accumulation in the Aorta of Dyslipidemic Mice

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