title: Central Agonism of GPR120 Acutely Inhibits Food Intake and Food Reward and Chronically Suppresses Anxiety-Like Behavior in Mice.
abstract: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (ω-3) polyunsaturated fatty acids. Increasing central ω-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior.
  
  
  
  Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 µM) or continuous 2-week infusion (1 µM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test.
  
  
  
  GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet.
  
  
  
  Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety.
authors.affiliation: CRCHUM & Montreal Diabetes Research Center (Drs Auguste, Fisette, and Fernandes, Ms Hryhorczuk, and Drs Poitout, Alquier, and Fulton); Department of Nutrition (Drs Auguste, Fisette, and Fulton), Department of Physiology (Dr Fernandes and Ms Hryhorczuk), and Department of Medicine (Drs Poitout and Alquier), Faculty of Medicine, Université de Montréal, QC, Canada. stephanie.fulton@umontreal.ca.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Auguste
authors.affiliation: CRCHUM & Montreal Diabetes Research Center (Drs Auguste, Fisette, and Fernandes, Ms Hryhorczuk, and Drs Poitout, Alquier, and Fulton); Department of Nutrition (Drs Auguste, Fisette, and Fulton), Department of Physiology (Dr Fernandes and Ms Hryhorczuk), and Department of Medicine (Drs Poitout and Alquier), Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fisette
authors.affiliation: CRCHUM & Montreal Diabetes Research Center (Drs Auguste, Fisette, and Fernandes, Ms Hryhorczuk, and Drs Poitout, Alquier, and Fulton); Department of Nutrition (Drs Auguste, Fisette, and Fulton), Department of Physiology (Dr Fernandes and Ms Hryhorczuk), and Department of Medicine (Drs Poitout and Alquier), Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Fernandes
authors.affiliation: CRCHUM & Montreal Diabetes Research Center (Drs Auguste, Fisette, and Fernandes, Ms Hryhorczuk, and Drs Poitout, Alquier, and Fulton); Department of Nutrition (Drs Auguste, Fisette, and Fulton), Department of Physiology (Dr Fernandes and Ms Hryhorczuk), and Department of Medicine (Drs Poitout and Alquier), Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Cécile
authors.initials: C
authors.lastname: Hryhorczuk
authors.affiliation: CRCHUM & Montreal Diabetes Research Center (Drs Auguste, Fisette, and Fernandes, Ms Hryhorczuk, and Drs Poitout, Alquier, and Fulton); Department of Nutrition (Drs Auguste, Fisette, and Fulton), Department of Physiology (Dr Fernandes and Ms Hryhorczuk), and Department of Medicine (Drs Poitout and Alquier), Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Poitout
authors.affiliation: CRCHUM & Montreal Diabetes Research Center (Drs Auguste, Fisette, and Fernandes, Ms Hryhorczuk, and Drs Poitout, Alquier, and Fulton); Department of Nutrition (Drs Auguste, Fisette, and Fulton), Department of Physiology (Dr Fernandes and Ms Hryhorczuk), and Department of Medicine (Drs Poitout and Alquier), Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Alquier
authors.affiliation: CRCHUM & Montreal Diabetes Research Center (Drs Auguste, Fisette, and Fernandes, Ms Hryhorczuk, and Drs Poitout, Alquier, and Fulton); Department of Nutrition (Drs Auguste, Fisette, and Fulton), Department of Physiology (Dr Fernandes and Ms Hryhorczuk), and Department of Medicine (Drs Poitout and Alquier), Faculty of Medicine, Université de Montréal, QC, Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fulton
mesh_terms: D000818:Animals; D001007:Anxiety / Q000517:prevention & control*; D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000096:biosynthesis / Q000502:physiology*; D012201:Reward; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001572:Benzofurans; C498007:FFAR4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D013450:Sulfones; C557331:TAK-875
keywords: FFAR4; GPCR; appetite; fatty acids; mood