TY - JOUR
T1 - Activation of short and long chain fatty acid sensing machinery in the ileum lowers glucose production in vivo
AU - Zadeh-Tahmasebi, Melika
AU - Duca, Frank A.
AU - Rasmussen, Brittany A.
AU - Bauer, Paige V.
AU - Côté, Clémence D.
AU - Filippi, Beatrice M.
AU - Lam, Tony K.T.
N1 - Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/4/15
Y1 - 2016/4/15
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M116.718460
DO - 10.1074/jbc.M116.718460
M3 - Article
C2 - 26896795
AN - SCOPUS:84965065077
SN - 0021-9258
VL - 291
SP - 8816
EP - 8824
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 16
ER -