Activation of Short and Long Chain Fatty Acid Sensing Machinery in the Ileum Lowers Glucose Production in Vivo.

The Journal of Biological Chemistry
Melika Zadeh-TahmasebiTony K T Lam

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.

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Citations

Aug 9, 2016·The Journal of Endocrinology·Paige V Bauer, Frank A Duca
Apr 10, 2017·Molecular Aspects of Medicine·Vance L AlbaughCharles R Flynn
Feb 3, 2018·BioMed Research International·Blandina Bernal-MoralesCarlos M Contreras
May 16, 2018·Nature Reviews. Nephrology·Tao YangMohan K Raizada
Feb 6, 2019·Metabolic Syndrome and Related Disorders·Marzieh Salehi, Jonathan Q Purnell
Feb 6, 2018·Journal of Developmental Origins of Health and Disease·M LemaireS Blat
May 16, 2018·Journal of Pediatric Gastroenterology and Nutrition·Satish C Kalhan
Jan 4, 2017·The Journal of Clinical Investigation·Daniel A WinerTony K T Lam
Dec 3, 2020·Critical Reviews in Food Science and Nutrition·Yao YaoCaihong Zheng
Dec 15, 2020·American Journal of Physiology. Endocrinology and Metabolism·Jonathan D Schertzer, Tony K T Lam
Feb 12, 2021·Nature Communications·Frank A DucaTony K T Lam
May 28, 2019·Journal of Agricultural and Food Chemistry·Zheng ZhangXiangna Zhao
Aug 16, 2021·Journal of Microbiological Methods·Marissa A Lopez-PierJohn P Konhilas
Oct 23, 2021·Annual Review of Medicine·Elizabeth J HowardFrank A Duca

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