Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites.
Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites.
复制标题
生酮饮食诱导小鼠葡萄糖不耐受和脂质积累，并改变肠道微生物群和代谢物
DOI：
10.1128/mbio.03601-20
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发表时间：
2021-03-30
期刊：
影响因子：
6.4
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Li Y;Yang X;Zhang J;Jiang T;Zhang Z;Wang Z;Gong M;Zhao L;Zhang C
具有极高脂肪和极低碳水化合物水平的生酮饮食在当今社会非常流行。虽然生酮饮食对癫痫和神经退行性疾病有有益的作用，但生酮饮食如何影响宿主的糖脂代谢和肠道微生物群仍需进一步研究。摘要生酮饮食（KD）可以诱导肠道微生物群的变化，对癫痫和几种神经退行性疾病有好处。然而，KD对葡萄糖和脂质代谢的影响仍不确定。使用小鼠试验中常用的两种生酮饮食配方（含89.5%脂肪的KDR和含91.3%脂肪的KDH），我们发现KDR而不是KDH诱导胰岛素抵抗和破坏葡萄糖稳态，而KDH在小鼠中诱导更多的脂肪积累。进一步研究发现KD影响糖代谢，糖代谢与脂肪来源有关，而脂肪来源和脂肪比例均影响脂代谢。在人类研究中广泛使用的KD仍然诱导小鼠胰岛素抵抗和脂肪积累。此外，KDs改变了小鼠的肠道微生物群和代谢物，并且饮食中脂肪的来源和比例分别改变了与葡萄糖耐受不良和脂质积累相关的参数相关的特定细菌和代谢物的丰度。总体而言，我们的研究表明，KDs诱导的代谢紊乱与膳食中脂肪的来源和比例密切相关，这可能与肠道微生物群和代谢产物的变化有关。重要性具有极高脂肪和极低碳水化合物水平的生酮饮食在当今社会非常流行。虽然生酮饮食对癫痫和神经退行性疾病有有益的作用，但生酮饮食如何影响宿主的糖脂代谢和肠道微生物群仍需进一步研究。在这里，我们调查了两种常用于小鼠试验的生酮饮食对小鼠代谢表型、肠道微生物群和代谢物的影响。我们发现，两种生酮饮食都损害了小鼠的葡萄糖和脂质代谢，这可能是由于饮食中脂肪的来源和比例。这项工作强调了葡萄糖和脂质代谢紊乱的潜在风险，以及在使用生酮饮食减肥和治疗疾病时评估饮食中脂肪来源和比例的重要性。
The ketogenic diet with extremely high fat and very low carbohydrate levels is very popular in society today. Although it has beneficial effects on epilepsy and neurodegenerative diseases, how ketogenic diets impact host glucose and lipid metabolism and gut microbiota still needs further investigation. ABSTRACT The ketogenic diet (KD), which can induce changes in gut microbiota, has shown benefits for epilepsy and several neurodegenerative diseases. However, the effects of a KD on glucose and lipid metabolism remain inconclusive. Using two formulas of ketogenic diets (KDR with 89.5% fat and KDH with 91.3% fat), which are commonly used in mouse trials, we found that KDR but not KDH induced insulin resistance and damaged glucose homeostasis, while KDH induced more fat accumulation in mice. Further study showed that KD impacted glucose metabolism, which was related to the sources of fat, while both the sources and proportions of fat affected lipid metabolism. And the KD widely used in human studies still induced insulin resistance and fat accumulation in mice. Moreover, KDs changed the gut microbiota and metabolites in mice, and the sources and proportions of fat in the diets respectively changed the abundance of specific bacteria and metabolites which were correlated with parameters related to glucose intolerance and lipid accumulation. Overall, our study demonstrated that the metabolic disorders induced by KDs are closely related to the source and proportion of fat in the diet, which may be associated with the changes of the gut microbiota and metabolites. IMPORTANCE The ketogenic diet with extremely high fat and very low carbohydrate levels is very popular in society today. Although it has beneficial effects on epilepsy and neurodegenerative diseases, how ketogenic diets impact host glucose and lipid metabolism and gut microbiota still needs further investigation. Here, we surveyed the effects of two ketogenic diets which are commonly used in mouse trials on metabolic phenotypes, gut microbiota, and metabolites in mice. We found that both ketogenic diets impaired glucose and lipid metabolism in mice, and this may be due to the sources and proportions of fat in the diets. This work highlights the potential risk of glucose and lipid metabolism disorders and the importance of evaluating the sources and proportions of fat in the diets, when using ketogenic diets for weight loss and the treatment of diseases.