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  • In summary we show that PE significantly ameliorate HCD indu

    2020-02-14

    In summary, we show that PE significantly ameliorate HCD-induced atherosclerosis in apoE−/− mice. Dietary fiber may influence the intestinal microbiota and thus the circulating levels of SCFAs. SCFAs, such as butyrate, inhibit cholesterol uptake and promote cholesterol excretion from enterocytes. Our findings shed new light on the role of butyrate and uncover a new mechanism of soluble dietary fiber metabolites in preventing the progression of atherosclerotic vascular disease.
    Authors\' contributions
    Conflict of interest
    Acknowledgments We also acknowledge the financial support from the National Natural Science Foundation of China (No. 81573152).
    Introduction The role of lifestyle patterns in the prevention/treatment of CVD has been extensively reviewed with most evidence showing that dietary factors, levels and types of physical activity, and tobacco cessation influence atherogenesis directly or through their effects on traditional risk factors and can also be used in the management of hypercholesterolemia. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels have been the primary targets of dyslipidemia therapy, precisely because they can be modified by lifestyle changes and drug therapies [1]. A novel strategy to complement the classical lipid profile determination (TC; LDL-C; high-density lipoprotein cholesterol (HDL-C); triglyceride (TG)) may be the analysis of the whole-body cholesterol homeostasis through the use of noncholesterol sterols (NCS) as surrogate markers of cholesterol metabolism. The circulating levels of NCS have been shown to correlate with the absolute cholesterol synthesis and Boc-D-Asp(OtBu)-OH.DCHA sale levels measured by the standard gold radio and stable isotopic methods [2], [3], [4]. The ease with which NCS can be measured compared to the complicated nature of more invasive isotopic methods has led to its wide use for the measurement and characterization of cholesterol metabolism across studies [5], [6], [7]. Among the cholesterol precursors, squalene, desmosterol, and lathosterol have been used as surrogate markers of cholesterol synthesis [3], [4], [8], and serum plant sterols (PS), mainly campesterol and sitosterol, and cholestanol, a 5α-saturated cholesterol derivative, as surrogate markers of cholesterol absorption [9]. Elevated cholesterol synthesis and reduced absorption have been reported in individuals with type 2 diabetes or hyperglycemia and have been associated with insulin resistance in cross-sectional studies [10], [11], [12], [13], [14]. Furthermore, several studies of NCS have described its association to established risk factors of CVD [15], [16]. Matthan and colleagues have documented in patients with CAD that LDL-C concentrations were positively associated with cholesterol synthesis markers and negatively associated with cholesterol absorption markers [16]. Available data of the prognostic value of the cholesterol homeostasis markers on CVD events are still inconsistent [17]. More recently, Hyanek et al. evaluated the clinical practical use of NCS, showing that extending the laboratory lipid spectrum scan through routine determination of NCS improves the differential diagnosis of heterozygous familial hypercholesterolemia (in children and adolescents) and the titration of therapeutic statin doses and makes monitoring and/or treatment more precise [18].
    Material and methods
    Results
    Discussion In our study, the average concentrations of the cholesterol absorption markers were higher than those of the synthesis markers, in accordance with Matthan et al [17]. In terms of the cholesterol synthesis markers, statistical significance was only found for lathosterol, but not for desmosterol, which is in accordance with Nissinen and colleagues [25], who showed that lathosterol appears to be the most reliable surrogate marker for cholesterol synthesis. Consistent with some of the prior data available [26], [27], on average, compared with men, women had lower concentrations of all synthesis markers assessed, indicating that, in women, the neo-synthesis of cholesterol is physiologically lower. These findings should also indicate a lower activity and expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), the rate-limiting enzyme in cholesterol biosynthesis. In accordance with prior reports, the markers of cholesterol synthesis and absorption showed the expected inverse associations, reflecting an apparent compensatory change in the cholesterol homeostasis metabolism [9], [15], [27], [28]. Compared with men, women had significantly higher concentrations of campesterol and sitosterol, but not of cholestanol; the exact physiological mechanisms that account for this association between serum cholestanol level and the fractional cholesterol absorption are not yet fully understood [3]. These differences on the basis of sex were not explained by differences in BMI, except for campesterol and LDL-C.