title: High-fat diet changes the temporal profile of GLP-1 receptor-mediated hypophagia in rats.
abstract: Overconsumption of a high-fat diet promotes weight gain that can result in obesity and associated comorbidities, including Type 2 diabetes mellitus. Consumption of a high-fat diet also alters gut-brain communication. Glucagon-like peptide 1 (GLP-1) is an important gastrointestinal signal that modulates both short- and long-term energy balance and is integral in maintenance of glucose homeostasis. In the current study, we investigated whether high-fat diets (40% or 81% kcal from fat) modulated the ability of the GLP-1 receptor (GLP-1r) agonists exendin-4 (Ex4) and liraglutide to reduce food intake and body weight. We observed that rats maintained on high-fat diets had a delayed acute anorexic response to peripheral administration of Ex4 or liraglutide compared with low-fat diet-fed rats (17% kcal from fat). However, once suppression of food intake in response to Ex4 or liraglutide started, the effect persisted for a longer time in the high-fat diet-fed rats compared with low-fat diet-fed rats. In contrast, centrally administered Ex4 suppressed food intake similarly between high-fat diet-fed and low-fat diet-fed rats. Chronic consumption of a high-fat diet did not change the pharmacokinetics of Ex4 but increased intestinal Glp1r expression and decreased hindbrain Glp1r expression. Taken together, these findings demonstrate that dietary composition alters the temporal profile of the anorectic response to exogenous GLP-1r agonists.
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH 45327, USA.
authors.forename: Joram D
authors.initials: JD
authors.lastname: Mul
authors.forename: Denovan P
authors.initials: DP
authors.lastname: Begg
authors.forename: Jason G
authors.initials: JG
authors.lastname: Barrera
authors.forename: Bailing
authors.initials: B
authors.lastname: Li
authors.forename: Emily K
authors.initials: EK
authors.lastname: Matter
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.forename: Darleen A
authors.initials: DA
authors.lastname: Sandoval
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology; D000069450:Liraglutide; D008297:Male; D044342:Malnutrition / Q000139:chemically induced / Q000503:physiopathology*; D023421:Models, Animal; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018027:Receptors, Glucagon / Q000819:agonists* / Q000502:physiology*; D014688:Venoms / Q000009:adverse effects / Q000494:pharmacology
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D005947:Glucose
keywords: exendin-4; food intake; glucagon-like peptide 1; liraglutide; obesity