title: The endocrine disrupting potential of monosodium glutamate (MSG) on secretion of the glucagon-like peptide-1 (GLP-1) gut hormone and GLP-1 receptor interaction.
abstract: Monosodium glutamate (MSG) is a suspected obesogen with epidemiological evidence positively correlating consumption to increased body mass index and higher prevalence of metabolic syndrome. ELISA and high content analysis (HCA) were employed to examine the disruptive effects of MSG on the secretion of enteroendocrine hormone glucagon-like peptide-1 (GLP-1) and GLP-1 receptor (GLP-1R), respectively. Following 3h MSG exposure of the enteroendocrine pGIP/neo: STC-1 cell line model (500μg/ml) significantly increased GLP-1 secretion (1.8 fold; P≤0.001), however, 72h exposure (500μg/ml) caused a 1.8 fold decline (P≤0.05). Also, 3h MSG exposure (0.5-500μg/ml) did not induce any cytotoxicity (including multiple pre-lethal markers) but 72h exposure at 250-500μg/ml, decreased cell number (11.8-26.7%; P≤0.05), increased nuclear area (23.9-29.8%; P≤0.001) and decreased mitochondrial membrane potential (13-21.6%; P≤0.05). At 500μg/ml, MSG increased mitochondrial mass by 16.3% (P≤0.01). MSG did not agonise or antagonise internalisation of the GLP-1R expressed recombinantly in U2OS cells, following GLP-1 stimulation. In conclusion, 72h exposure of an enteroendocrine cell line at dietary levels of MSG, results in pre-lethal cytotoxicity and decline in GLP-1 secretion. These adverse events may play a role in the pathogenesis of obesity as outlined in the obesogen hypothesis by impairing GLP-1 secretion, related satiety responses and glucose-stimulated insulin release.
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Maeve
authors.initials: M
authors.lastname: Shannon
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Green
authors.affiliation: Department of Molecular and Cell Biology, University of Leicester, Leicester, England, United Kingdom.
authors.forename: Gary
authors.initials: G
authors.lastname: Willars
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Jodie
authors.initials: J
authors.lastname: Wilson
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Natalie
authors.initials: N
authors.lastname: Matthews
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lamb
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Gillespie
authors.affiliation: Institute for Global Food Security, School of Biological Sciences, Queen's University, Belfast, Northern Ireland, United Kingdom. Electronic address: l.connolly@qub.ac.uk.
authors.forename: Lisa
authors.initials: L
authors.lastname: Connolly
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D012970:Sodium Glutamate / Q000633:toxicity*; D013997:Time Factors
chemical_list: D052244:Endocrine Disruptors; D000067757:Glucagon-Like Peptide-1 Receptor; D052216:Glucagon-Like Peptide 1; D012970:Sodium Glutamate
keywords: Diabetes; GLP-1; High content analysis; In vitro bioassays; Monosodium glutamate; Obesity