Intermittent calorie restriction largely counteracts the adverse health effects of a moderate-fat diet in aging C57BL/6J mice

Calorie restriction (CR) has been shown to extend life- and health-span in model species. For most humans, a life-long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can 1) provide long-term beneficial effects and 2) counteract diet-induced obesity in male aging mice. In this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate-fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight and liver health markers in male 24-month-old mice. Hepatic gene expression profiles of INT-exposed animals appeared much more comparable to CR than to MF-exposed mice. At 12 months of age, a subgroup of MF-exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24-month-old diet switch mice were highly similar to the INT-exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life. Weekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet. Male C57Bl/6J mice were divided to 3 dietary intervention groups: Control (AIN-93W), 30% calorie restriction (CR; AIN-93W-CR) and medium fat (MF; AIN-93W-MF; 25% energy from fat). Dietary interventions started at the age of 9 weeks and sacrifice was performed at the age of 6, 12, 24 and 28 months. We performed various measurements on metabolic parameters and gene expression analysis. This entry represents the microarray data. The array data from the 6-, 12- and 24-month-old mice exposed to the Control, CR and MF diet have been published before, and are also available under GEO accession number GSE84495.

热量限制（Calorie restriction，CR）已被证实可延长模式生物的寿命与健康寿命。但对于绝大多数人类而言，终生坚持热量限制饮食过于严苛，难以依从。本研究旨在探究每周间歇性热量限制能否达成两大目标：其一，产生长期有益效应；其二，缓解老年雄性小鼠因饮食诱导产生的肥胖。本研究中，我们将C57Bl/6J小鼠暴露于间歇性饮食（intermittent diet，INT）方案长达24个月，该方案每周交替进行对照饮食的热量限制与自由采食（ad libitum）中脂（moderate-fat，MF）喂养。这种每周间歇性热量限制显著缓解了中脂饮食对24月龄雄性小鼠的死亡率、体重及肝脏健康标志物产生的不良影响。间歇性饮食干预小鼠的肝脏基因表达谱与热量限制组小鼠更为相似，而非中脂饮食组小鼠。在小鼠12月龄时，我们将一部分中脂饮食组的小鼠转至间歇性饮食干预方案。24月龄时，饮食转换组小鼠的肝脏基因表达谱与全程间歇性饮食干预小鼠高度相似。但仍有少量基因在小鼠生命早期的中脂饮食暴露期间发生了持续性表达改变。每周间歇性热量限制可在很大程度上（但并非完全）逆转中脂饮食所引发的不良影响。本研究将雄性C57Bl/6J小鼠分为3组饮食干预组：对照组（Control，AIN-93W）、30%热量限制组（30% calorie restriction，CR；AIN-93W-CR）以及中脂组（medium fat，MF；AIN-93W-MF，脂肪供能占比25%）。饮食干预于小鼠9周龄时启动，分别在6、12、24及28月龄时对小鼠实施安乐死采样。我们对代谢相关参数进行了多项检测，并开展了基因表达分析。本数据集条目对应的即为微阵列（microarray）检测数据。此前已有研究发表了暴露于对照组、热量限制组及中脂饮食组的6、12、24月龄小鼠的芯片微阵列数据，该部分数据亦可通过GEO登录号GSE84495获取。