Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice
Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice
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DOI：
10.1152/ajpendo.00363.2015
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发表时间：
2016-06-01
影响因子：
5.1
通讯作者：
Kristiansen, Karsten
中科院分区：
文献类型：
--
作者：
Kiilerich, Pia;Myrmel, Lene Secher;Kristiansen, Karsten
在雌性C57BL/6J小鼠的整个生命过程中，他们被喂以常规的低脂肪饮食或高脂肪饮食，或高或低的蛋白质/蔗糖比率，以考察它们对肥胖发展、肠道微生物区系和生存的长期影响。与低脂肪饮食相比，摄入低蛋白质/蔗糖比例的高脂肪饮食会导致肥胖并降低存活率。相比之下，摄入高蛋白质/蔗糖比例的高脂肪饮食会减缓终生体重增加和脂肪组织扩张，与低脂肪喂养的小鼠相比，存活时间没有明显改变。我们的发现支持了这样一种观点，即高脂肪/高蔗糖喂养导致的存活率下降与肥胖的发生有关。经qPCR进一步验证的数字基因表达分析表明，随着时间的推移，蛋白质/蔗糖比例调节了肝脏和脂肪组织中的整体基因表达，影响了与新陈代谢和炎症相关的途径。利用小鼠肠道芯片对粪便细菌DNA的分析显示，肠道微生物区系的组成与宿主年龄和食物脂肪含量有关，但与蛋白质/蔗糖比例无关。因此，饮食脂肪而不是蛋白质/蔗糖比率或肥胖是形成肠道微生物区系的主要驱动因素，而高脂肪饮食对生存的影响取决于蛋白质/蔗糖比率。
Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio.