Alphonse Peter A S, Jones Peter J H
Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada.
Richardson Centre for Functional Foods and Nutraceuticals (RCFFN), University of Manitoba, 196, Innovation Drive, SmartPark, Winnipeg, MB, R3T 2N2, Canada.
Lipids. 2016 May;51(5):519-36. doi: 10.1007/s11745-015-4096-7. Epub 2015 Nov 30.
Hypercholesterolemia is a major risk factor for cardiovascular disease. Cholesterol homeostasis in the body is governed by the interplay between absorption, synthesis, and excretion or conversion of cholesterol into bile acids. A reciprocal relationship between cholesterol synthesis and absorption is known to regulate circulating cholesterol in response to dietary or therapeutic interventions. However, the degree to which these factors affect synthesis and absorption and the extent to which one vector shifts in response to the other are not thoroughly understood. Also, huge inter-individual variability exists in the manner in which the two systems act in response to any cholesterol-lowering treatment. Various factors are known to account for this variability and in light of recent experimental advances new players such as gene-gene interactions, gene-environmental effects, and gut microbiome hold immense potential in offering an explanation to the complex traits of inter-individual variability in human cholesterol metabolism. In this context, the objective of the present review is to provide an overview on cholesterol metabolism and discuss the role of potential factors such as genetics, epigenetics, epistasis, and gut microbiome, as well as other regulators in modulating cholesterol metabolism, especially emphasizing the reciprocal relationship between cholesterol synthesis and absorption. Furthermore, an evaluation of the implications of this push-pull mechanism on cholesterol-lowering strategies is presented.
高胆固醇血症是心血管疾病的主要危险因素。体内胆固醇的稳态受胆固醇吸收、合成以及排泄或转化为胆汁酸之间相互作用的调控。已知胆固醇合成与吸收之间的相互关系可根据饮食或治疗干预来调节循环胆固醇水平。然而，这些因素对合成和吸收的影响程度以及一个因素随另一个因素变化的程度尚未完全明确。此外，在任何降胆固醇治疗中，这两个系统的作用方式存在巨大的个体差异。已知多种因素可解释这种变异性，鉴于最近的实验进展，诸如基因 - 基因相互作用、基因 - 环境效应和肠道微生物群等新因素在解释人类胆固醇代谢个体差异的复杂特征方面具有巨大潜力。在此背景下，本综述的目的是概述胆固醇代谢，并讨论遗传学、表观遗传学、上位性和肠道微生物群等潜在因素以及其他调节因子在调节胆固醇代谢中的作用，尤其强调胆固醇合成与吸收之间的相互关系。此外，还对这种推拉机制对降胆固醇策略的影响进行了评估。
