{"title":"Free fatty acid receptor 4 modulates dietary sugar preference via the gut microbiota","authors":"Tingting Zhang, Wei Wang, Jiayu Li, Xianlong Ye, Zhe Wang, Siyuan Cui, Shiwei Shen, Xinmiao Liang, Yong Q. Chen, Shenglong Zhu","doi":"10.1038/s41564-024-01902-8","DOIUrl":null,"url":null,"abstract":"<p>Sugar preference is a key contributor to the overconsumption of sugar and the concomitant increase in the incidence of diabetes. However, the exact mechanism of its development remains ambiguous. Here we show that the expression of free fatty acid receptor Ffar4, a receptor for long-chain fatty acids, is decreased in patients and mouse models with diabetes, which is associated with high sugar intake. Deletion of intestinal Ffar4 in mice resulted in reduced gut <i>Bacteroides vulgatus</i> and its metabolite pantothenate, leading to dietary sugar preference. Pantothenate promoted the secretion of GLP-1 which inhibited sugar preference by stimulating hepatic FGF21 release, which in turn regulates energy metabolism. These findings uncover a previously unappreciated role of Ffar4 in negatively regulating sugar preference and suggest <i>B. vulgatus</i>-derived pantothenate as a potential therapeutic target for diabetes.</p>","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"75 1","pages":""},"PeriodicalIF":20.5000,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Microbiology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41564-024-01902-8","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
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Abstract
Sugar preference is a key contributor to the overconsumption of sugar and the concomitant increase in the incidence of diabetes. However, the exact mechanism of its development remains ambiguous. Here we show that the expression of free fatty acid receptor Ffar4, a receptor for long-chain fatty acids, is decreased in patients and mouse models with diabetes, which is associated with high sugar intake. Deletion of intestinal Ffar4 in mice resulted in reduced gut Bacteroides vulgatus and its metabolite pantothenate, leading to dietary sugar preference. Pantothenate promoted the secretion of GLP-1 which inhibited sugar preference by stimulating hepatic FGF21 release, which in turn regulates energy metabolism. These findings uncover a previously unappreciated role of Ffar4 in negatively regulating sugar preference and suggest B. vulgatus-derived pantothenate as a potential therapeutic target for diabetes.
期刊介绍：
Nature Microbiology aims to cover a comprehensive range of topics related to microorganisms. This includes:
Evolution: The journal is interested in exploring the evolutionary aspects of microorganisms. This may include research on their genetic diversity, adaptation, and speciation over time.
Physiology and cell biology: Nature Microbiology seeks to understand the functions and characteristics of microorganisms at the cellular and physiological levels. This may involve studying their metabolism, growth patterns, and cellular processes.
Interactions: The journal focuses on the interactions microorganisms have with each other, as well as their interactions with hosts or the environment. This encompasses investigations into microbial communities, symbiotic relationships, and microbial responses to different environments.
Societal significance: Nature Microbiology recognizes the societal impact of microorganisms and welcomes studies that explore their practical applications. This may include research on microbial diseases, biotechnology, or environmental remediation.
In summary, Nature Microbiology is interested in research related to the evolution, physiology and cell biology of microorganisms, their interactions, and their societal relevance.
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