SFEBES2021 Poster Presentations Metabolism, Obesity and Diabetes (78 abstracts)
Investigating 2-oleoylglycerol responsive neuronal pathways
Sijing Cheng , Mariana Norton , Anna Roberts , Aldara Martin Alonso , Phyllis Phuah , Emily Tulloch , Heloise Vinette , Kaa-Yung Ng , Bryn Owen , Aylin Hanyaloglu & Kevin Murphy
Imperial College London, London, United Kingdom
Dietary fat intake is an important source of energy and in excess can drive the development of obesity. Investigating how dietary fat intake alters neuronal activity in the brain and drives behavioural changes may help us understand the mechanisms behind high fat diet induced obesity. 2-oleoyglycerol (2-OG) is a naturally occurring unsaturated long chain fatty acid produced by fat digestion in the gut and a ligand of G protein-coupled receptor 119 (GPR119). Published data has shown that 2-OG increases glucagon-like peptide-1 (GLP-1) release in murine colonic crypt cultures and this effect is lost in crypts cultured from gpr119 knockout mice. Our data shows that 2-OG improves oral glucose tolerance in both lean and high fat diet induced obese mice possibly via incretins such as GLP-1. However, the neuronal responses and behavioural changes driven by intestinal 2-OG are still unclear. In addition to gut hormone signalling, the transduction of gastrointestinal luminal nutrient information to the brain is also mediated by the parasympathetic vagus nerve. The cell bodies of vagal afferent neurons reside within the nodose ganglia, which highly express GPR119. Our data shows that 2-OG increases intracellular calcium signalling in murine nodose ganglia neurons in vitro. The effects of oral administration of 2-OG or the synthetic GPR119 agonist AR231453 on neuronal activation were assessed by the immunostaining of c-Fos. The vagus nerve signals to specific regions of the brainstem, including the nucleus of the tractus solitarius (NTS). Oral administration of 2-OG to mice increased the number of c-Fos expressing cells in the NTS and the dorsal motor nucleus of the vagus (DMV). Because NTS and DMV are closely related to gastric motility and food preferences, we studied the effects of 2-OG on gastric emptying and food choice. Mapping 2-OG responsive gut-brain pathways may help to provide new therapeutic targets in obesity.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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