Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China (C.M., Y.G.); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China (C.M., Y.G.); Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, P. R. China (C.M., Y.G.); National Clinical Research Center for Geriatric Disorders,Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China (C.M., Y.G.); and Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas (C.D.K.).
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, P. R. China (C.M., Y.G.); Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, P. R. China (C.M., Y.G.); Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, P. R. China (C.M., Y.G.); National Clinical Research Center for Geriatric Disorders,Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China (C.M., Y.G.); and Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas (C.D.K.)
Drug Metab Dispos. 2021 Jan;49(1):62-71. doi: 10.1124/dmd.120.000166. Epub 2020 Oct 22.
Diet is an important factor for many diseases. Previous studies have demonstrated that several diets had remarkable effects on bile acid (BA) homeostasis, but no comprehensive information for both genders has been reported. Therefore, the current study characterized the nine most used laboratory animal diets fed to both genders of mice for a comparable evaluation of the topic. The results revealed that marked gender difference of BA homeostasis is ubiquitous in mice fed the various diets, and of the nine diets fed to mice, the atherogenic and calorie-restricted diets had the most marked effects on BA homeostasis, followed by the laboratory chow and essential fatty acid-deficient diets. More specifically, females had higher concentrations of total BAs in serum when fed six of the nine diets compared with male mice, and 26 of the 35 BA-related genes had marked gender difference in mice fed at least one diet. Although mice fed the calorie-restricted and atherogenic diets had increased BA, which was more pronounced in serum than liver, the intestinal farnesoid X nuclear receptor-fibroblast growth factor 15 axis changed in the opposite direction and resulted in different hepatic expression patterns of Compared with AIN-93M purified diet, higher hepatic expression of multidrug resistance-associated protein 3 was the only alteration in mice fed the laboratory chow diet. The other diets had little or no effect on BA concentrations in the liver and plasma or in the expression of BA-related genes. This study indicates that gender, the atherogenic diet, and the calorie-restricted diet have the most marked effects on BA homeostasis. SIGNIFICANCE STATEMENT: Previous evidence suggested that various diets have effect on bile acid (BA) homeostasis; however, it is not possible to directly compare these findings, as they are all from different studies. The current study was the first to systematically investigate the influence of the nine most used experimental mouse diets on BA homeostasis and potential mechanism in both genders of mice and indicates that gender, the atherogenic diet, and the calorie-restricted diet have the most marked effects on BA homeostasis, which will aid future investigations.
饮食是许多疾病的重要因素。先前的研究表明,几种饮食对胆汁酸(BA)稳态有显著影响,但没有针对两性的综合信息。因此,本研究对两性小鼠最常用的九种实验动物饮食进行了特征描述,以便对该主题进行比较评估。结果表明,在所研究的九种饮食中,雄性和雌性小鼠的 BA 稳态存在明显的性别差异,在所研究的九种饮食中,致动脉粥样硬化饮食和热量限制饮食对 BA 稳态的影响最大,其次是实验室标准饲料和必需脂肪酸缺乏饮食。更具体地说,与雄性小鼠相比,雌性小鼠在摄入九种饮食中的六种饮食时血清中总胆汁酸浓度更高,在至少一种饮食中喂养的 35 种 BA 相关基因中有 26 种具有明显的性别差异。尽管热量限制饮食和致动脉粥样硬化饮食使 BA 增加,但血清中的 BA 增加更为明显,而法尼醇 X 核受体-成纤维细胞生长因子 15 轴则发生相反的变化,导致肝脏中的表达模式不同。与AIN-93M 纯化饮食相比,在摄入实验室标准饲料的小鼠中,多药耐药相关蛋白 3 的肝表达增加是唯一的变化。其他饮食对肝脏和血浆中的 BA 浓度或 BA 相关基因的表达几乎没有影响或没有影响。本研究表明,性别、致动脉粥样硬化饮食和热量限制饮食对 BA 稳态的影响最大。
先前的证据表明,各种饮食对胆汁酸(BA)稳态有影响;然而,由于它们都来自不同的研究,因此不可能直接比较这些发现。本研究首次系统地研究了九种最常用的实验小鼠饮食对雌雄小鼠 BA 稳态的影响及其潜在机制,表明性别、致动脉粥样硬化饮食和热量限制饮食对 BA 稳态的影响最大,这将有助于未来的研究。