Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption.

Autor: Li X; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Yang J; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Zhou X; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Dai C; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Kong M; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Xie L; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Liu C; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China.; Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai, P.R. China., Liu Y; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Li D; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Ma X; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Dai Y; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, P.R. China., Sun Y; Masonic Medical Research Institute, Utica, NY, USA., Jian Z; Department of Radiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China., Guo X; Institute for Immunology, Tsinghua University, Beijing, P.R. China., Lin X; Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, P.R. China.; Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, P.R. China., Li Y; Bio-Med Big Data Center, Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, P.R. China.; Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai, P.R. China.; School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R. China., Sun L; Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, P.R. China., Liu X; Department of Epidemiology and Biostatistics, School of Public Health, Global Health Institute, Xi'an Jiaotong University Health Science Center, Xi'an, P.R. China., Jin L; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Tang H; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China., Zheng Y; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China. yan_zheng@fudan.edu.cn.; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai, P.R. China. yan_zheng@fudan.edu.cn.; Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, P.R. China. yan_zheng@fudan.edu.cn., Hong S; State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, P.R. China. shangyu_hong@fudan.edu.cn.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2024 Jul; Vol. 6 (7), pp. 1397-1414. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1038/s42255-024-01072-1
Abstrakt: The low-carbohydrate ketogenic diet (KD) has long been practiced for weight loss, but the underlying mechanisms remain elusive. Gut microbiota and metabolites have been suggested to mediate the metabolic changes caused by KD consumption, although the particular gut microbes or metabolites involved are unclear. Here, we show that KD consumption enhances serum levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA) in mice to decrease body weight and fasting glucose levels. Mechanistically, KD feeding decreases the abundance of a bile salt hydrolase (BSH)-coding gut bacterium, Lactobacillus murinus ASF361. The reduction of L. murinus ASF361 or inhibition of BSH activity increases the circulating levels of TDCA and TUDCA, thereby reducing energy absorption by inhibiting intestinal carbonic anhydrase 1 expression, which leads to weight loss. TDCA and TUDCA treatments have been found to protect against obesity and its complications in multiple mouse models. Additionally, the associations among the abovementioned bile acids, microbial BSH and metabolic traits were consistently observed both in an observational study of healthy human participants (n = 416) and in a low-carbohydrate KD interventional study of participants who were either overweight or with obesity (n = 25). In summary, we uncover a unique host-gut microbiota metabolic interaction mechanism for KD consumption to decrease body weight and fasting glucose levels. Our findings support TDCA and TUDCA as two promising drug candidates for obesity and its complications in addition to a KD.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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