Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 291, Issue 16, Pages 8816-8824Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.718460
Keywords
fatty acid; glucose; glucose metabolism; intestine; lipid signaling
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Funding
- Canadian Institutes of Health Research Foundation [FDN-143204]
- Banting and Best Diabetes Centre graduate studentship
- Vanier Canada scholarship
- Ontario Graduate Scholarship
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Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fatty acids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fatty acid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo. We further demonstrate that an ileal glucagon-like peptide-1 receptor-dependent neuronal network is necessary for ileal propionate and long chain fatty acid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fatty acid sensing machinery in the ileum to regulate glucose homeostasis.
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