title: Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo.
abstract: 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.
authors.affiliation: From the Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario M5G 1L7, the Departments of Physiology and.
authors.forename: Melika
authors.initials: M
authors.lastname: Zadeh-Tahmasebi
authors.affiliation: From the Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario M5G 1L7.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Duca
authors.affiliation: From the Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario M5G 1L7, the Departments of Physiology and.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Rasmussen
authors.affiliation: From the Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario M5G 1L7, the Departments of Physiology and.
authors.forename: Paige V
authors.initials: PV
authors.lastname: Bauer
authors.affiliation: From the Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario M5G 1L7, the Departments of Physiology and.
authors.forename: Clémence D
authors.initials: CD
authors.lastname: Côté
authors.affiliation: From the Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario M5G 1L7.
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Filippi
authors.affiliation: From the Toronto General Research Institute and Department of Medicine, UHN, Toronto, Ontario M5G 1L7, the Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, and the Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario M5G 2C4, Canada tony.lam@uhnres.utoronto.ca.
authors.forename: Tony K T
authors.initials: TK
authors.lastname: Lam
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005227:Fatty Acids; D052216:Glucagon-Like Peptide 1; D005947:Glucose
keywords: fatty acid; glucose; glucose metabolism; intestine; lipid signaling