A weekly alternating diet between caloric restriction and medium fat protects the liver from NAFLD in middle aged C57BL/6J mice

SCOPE: We investigated whether a novel dietary intervention consisting of an every-other-week calorie-restricted diet could prevent nonalcoholic fatty liver disease (NAFLD) development induced by a medium-fat (MF) diet. METHODS AND RESULTS: Nine-week-old male C57BL/6J mice received either a (i) control (C), (ii) 30E% calorie restricted (CR), (iii) MF (25E% fat), or (iv) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight. CONCLUSIONS: Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevents the development of NAFLD in 12-month-old male C57BL/6J mice. Male C57Bl/6J mice were divided to 4 dietary intervention groups: Control (AIN-93W), 30% calorie restriction (CR; AIN-93W-CR), medium fat (MF; AIN-93W-MF; 25% energy from fat) and intermittent diet (INT; weekly alternating diet between AIN-93W-MF ad lib and 40% CR of AIN-93W). We performed various measurements on metabolic parameters and gene expression analysis on the liver. This entry represents the microarray data of the liver gene expression of each mouse.

研究范围：本研究旨在探讨以隔周热量限制饮食为代表的新型膳食干预手段，能否预防由中等脂肪膳食（medium-fat, MF）诱导的非酒精性脂肪性肝病（nonalcoholic fatty liver disease, NAFLD）发生。方法与结果：选取9周龄雄性C57BL/6J小鼠，分别接受以下4种膳食干预：(i) 对照组（C）、(ii) 30%能量占比热量限制组（30E% calorie restricted, CR）、(iii) 中等脂肪膳食组（MF，脂肪供能占比25E%）以及(iv) 间歇性饮食组（intermittent, INT）——该组每周交替采用40%能量占比热量限制膳食与自由进食的中等脂肪膳食，直至小鼠12月龄时处死。本研究检测了非酒精性脂肪性肝病（NAFLD）的代谢、形态学与分子特征。结果显示，间歇性饮食组与持续热量限制组一样，可带来健康的代谢与形态学表型：小鼠糖耐量正常、肝甘油三酯含量较低、血浆丙氨酸氨基转移酶水平较低。与之相反，体重较高的对照组与中等脂肪膳食组小鼠出现了非酒精性脂肪性肝病（NAFLD）的典型征象。不过，间歇性饮食组小鼠的基因表达谱与热量限制组存在差异，且与体重相当的对照组及中等脂肪膳食组小鼠更为相似。结论：本研究表明，间歇性饮食可维持代谢健康，逆转中等脂肪膳食带来的不良影响，从而在12月龄雄性C57BL/6J小鼠中有效预防非酒精性脂肪性肝病（NAFLD）的发生。本实验将雄性C57Bl/6J小鼠分为4个膳食干预组：对照组（AIN-93W）、30%热量限制组（CR；AIN-93W-CR）、中等脂肪膳食组（MF；AIN-93W-MF；脂肪供能占比25%）以及间歇性饮食组（INT；每周交替采用自由进食的AIN-93W-MF膳食与40%热量限制的AIN-93W膳食）。我们对代谢参数进行了多项检测，并对肝脏组织开展了基因表达分析。本数据集条目对应每只小鼠肝脏基因表达的微阵列（microarray）数据。