title: Removal of high-fat diet after chronic exposure drives binge behavior and dopaminergic dysregulation in female mice.
abstract: A significant contributor to the obesity epidemic is the overconsumption of highly palatable, energy dense foods. Chronic intake of palatable foods is associated with neuroadaptations within the mesocorticolimbic dopamine system adaptations which may lead to behavioral changes, such as overconsumption or bingeing. We examined behavioral and molecular outcomes in mice that were given chronic exposure to a high-fat diet (HFD; 12weeks), with the onset of the diet either in adolescence or adulthood. To examine whether observed effects could be reversed upon removal of the HFD, animals were also studied 4weeks after a return to chow feeding. Most notably, female mice, particularly those exposed to HFD starting in adolescence, demonstrated the emergence of binge-like behavior when given restricted access to a palatable food. Further, changes in dopamine-related gene expression and dopamine content in the prefrontal cortex were observed. Some of these HFD-driven phenotypes reversed upon removal of the diet, whereas others were initiated by removal of the diet. These findings have implications for obesity management and interventions, as both pharmacological and behavioral therapies are often combined with dietary interventions (e.g., reduction in calorie dense foods).
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Jesse L
authors.initials: JL
authors.lastname: Carlin
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: McKee
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hill-Smith
authors.affiliation: Department of Psychiatry and Behavioral Neurosciences, College of Medicine, University of Cincinnati, Cincinnati, OH 45237, United States.
authors.forename: Nicola M
authors.initials: NM
authors.lastname: Grissom
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: George
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
authors.forename: Irwin
authors.initials: I
authors.lastname: Lucki
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Psychiatry and Behavioral Neurosciences, College of Medicine, University of Cincinnati, Cincinnati, OH 45237, United States. Electronic address: reyesta@ucmail.uc.edu.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Reyes
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002032:Bulimia / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004435:Eating; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009714:Nucleus Accumbens / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012201:Reward; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: C000600618:DRD2 protein, mouse; D050483:Dopamine Plasma Membrane Transport Proteins; C583261:Drd1 protein, mouse; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: adolescence; binge; dopamine; high-fat diet; reward; sex difference