低密度脂蛋白胆固醇（LDL-C）是心血管疾病防治的重要靶点，其血清水平受胆固醇代谢途径的调控及肠道菌群和短链脂肪酸的影响。以往研究缺乏直接比较不同膳食碳水化合物构成模式（高添加糖、高精制谷物和高全谷物模式）对LDL-C水平的影响。我们的研究表明，高胆固醇受试者在摄入高精制谷物膳食后，血清LDL-C及胆固醇吸收与合成标记物的水平高于摄入高添加糖和高全谷物膳食后的水平，但不同模式对调节LDL-C水平相关机制的影响尚不明确。本课题拟利用ApoE-/-小鼠开展以下研究：1）比较不同膳食碳水化合物构成模式对胆固醇吸收、合成和转化外排途径的关键控制点和转录因子水平的影响；2）比较不同模式对肠道菌群多样性与组成和短链脂肪酸水平的影响；3）分析胆固醇代谢途径的关键控制点和转录因子水平与肠道菌丰度以及短链脂肪酸水平之间的相关性。研究结果将阐明不同碳水化合物构成模式影响LDL-C水平的作用靶点和相关分子机制。

Low-density lipoprotein cholesterol (LDL-C) is an important target for the prevention and treatment of cardiovascular disease, and the serum concentrations of LDL-C can be regulated by cholesterol metabolism pathways and influenced by gut microbiota and short chain fatty acids. Prior studies that have directly compared the effects of different dietary carbohydrate patterns (high added sugar, high refined grain and high whole grain patterns) on serum LDL-C concentrations are extremely limited. Our previous study has reported that consumption of high refined grain diet resulted in higher concentrations of serum LDL-C as well as cholesterol absorption and synthesis markers compared with consumption of high added sugar and high whole grain diets in participants with hypercholesterolemia. However, the potential mechanisms underlying the differential effects of dietary carbohydrate patterns on serum LDL-C concentrations have not been investigated. In our current study, an ApoE-/- mouse model will be used to investigate the following objectives. We will first compare the effects of different dietary carbohydrate patterns on the levels of critical control points and transcription factors in cholesterol absorption, synthesis and excretion pathways. We will then compare the effects of different dietary carbohydrate patterns on the diversity and composition of gut microbiota and short chain fatty acids levels. In addition, we will analyze the correlations between levels of critical control points and transcription factors in cholesterol metabolism pathways and levels of gut bacteria and short chain fatty acids. The current study will identify the molecular targets and mechanisms underlying the differential effects of different dietary carbohydrate patterns on the regulation of serum LDL-C concentrations.