Activation of short and long chain fatty acid sensing machinery in the ileum lowers glucose production in vivo

Melika Zadeh-Tahmasebi, Frank A. Duca, Brittany A. Rasmussen, Paige V. Bauer, Clémence D. Côté, Beatrice M. Filippi, Tony K.T. Lam

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Evidence continuestoemerge detailing the myriadofways 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.

Original languageEnglish (US)
Pages (from-to)8816-8824
Number of pages9
JournalJournal of Biological Chemistry
Volume291
Issue number16
DOIs
StatePublished - Apr 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Zadeh-Tahmasebi, M., Duca, F. A., Rasmussen, B. A., Bauer, P. V., Côté, C. D., Filippi, B. M., & Lam, T. K. T. (2016). Activation of short and long chain fatty acid sensing machinery in the ileum lowers glucose production in vivo. Journal of Biological Chemistry, 291(16), 8816-8824. https://doi.org/10.1074/jbc.M116.718460