期刊
CELL METABOLISM
卷 24, 期 1, 页码 151-157出版社
CELL PRESS
DOI: 10.1016/j.cmet.2016.06.013
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资金
- Institut National de la Sante et de la Recherche Medicale
- University Lyon 1
- Swedish Research Council
- NovoNordisk foundation
- Torsten Soderberg's foundation
- Swedish Heart Lung Foundation
- Goran Gustafsson's foundation
- IngaBritt och Arne Lundberg's foundation
- Knut and Alice Wallenberg foundation
- Swedish Foundation for Strategic Research
- EMBO Long-Term Fellowship [ALTF 1305-2014, GA-2013-609409]
- NNF Center for Basic Metabolic Research [Bäckhed Group] Funding Source: researchfish
- Novo Nordisk Fonden [NNF13OC0008163] Funding Source: researchfish
Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN.
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