title: Reversal of dopamine system dysfunction in response to high-fat diet.
abstract: OBJECTIVE
  To test whether high-fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD.
  
  
  METHODS
  Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age-matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)-related genes by Real Time-quantitative PCR (RT-qPCR). DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT-qPCR.
  
  
  RESULTS
  After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region.
  
  
  CONCLUSIONS
  These data identify diminished DA tone after early-life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight-loss after diet intervention.
authors.affiliation: Department of Pharmacology, Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Jesselea
authors.initials: J
authors.lastname: Carlin
authors.forename: Tiffany E
authors.initials: TE
authors.lastname: Hill-Smith
authors.forename: Irwin
authors.initials: I
authors.lastname: Lucki
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Reyes
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019175:DNA Methylation; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012201:Reward; D012439:Saccharin / Q000008:administration & dosage; D013395:Sucrose / Q000008:administration & dosage; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D004041:Dietary Fats; D050483:Dopamine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D015102:3,4-Dihydroxyphenylacetic Acid; D013395:Sucrose; D012439:Saccharin; D004298:Dopamine