Li Yue, Yang Xin, Zhang Jing, Jiang Tianyi, Zhang Ziyi, Wang Zhiyi, Gong Mengxue, Zhao Liping, Zhang Chenhong
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Department of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition and Health, School of Environmental and Biological Sciences, Rutgers University, New Brunswick, New Jersey, USA.
mBio. 2021 Mar 30;12(2):e03601-20. doi: 10.1128/mBio.03601-20.
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. 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.
生酮饮食（KD）可引起肠道微生物群的变化，已显示出对癫痫和几种神经退行性疾病有益。然而，KD对葡萄糖和脂质代谢的影响仍无定论。我们使用了小鼠试验中常用的两种生酮饮食配方（脂肪含量为89.5%的KDR和脂肪含量为91.3%的KDH），发现KDR而非KDH会诱导胰岛素抵抗并破坏葡萄糖稳态，而KDH会使小鼠体内脂肪堆积更多。进一步研究表明，KD会影响葡萄糖代谢，这与脂肪来源有关，而脂肪的来源和比例均会影响脂质代谢。并且在人体研究中广泛使用的KD仍会诱导小鼠出现胰岛素抵抗和脂肪堆积。此外，KD改变了小鼠的肠道微生物群和代谢产物，饮食中脂肪的来源和比例分别改变了与葡萄糖不耐受和脂质堆积相关参数的特定细菌和代谢产物的丰度。总体而言，我们的研究表明，KD诱导的代谢紊乱与饮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。脂肪含量极高、碳水化合物水平极低的生酮饮食如今在社会上非常流行。尽管它对癫痫和神经退行性疾病有有益影响，但生酮饮食如何影响宿主的葡萄糖和脂质代谢以及肠道微生物群仍需进一步研究。在此，我们研究了小鼠试验中常用的两种生酮饮食对小鼠代谢表型、肠道微生物群和代谢产物的影响。我们发现两种生酮饮食都会损害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所致。这项工作凸显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进行减肥和疾病治疗时评估饮食中脂肪来源和比例的重要性。
