title: Effect of high-fat feeding on expression of genes controlling availability of dopamine in mouse hypothalamus.
abstract: OBJECTIVE
  Hypothalamic centers integrate external signals of nutrient availability and energy status and initiate responses to maintain homeostasis. Quantifying changes in hypothalamic gene expression in the presence of nutrient excess may identify novel responsive elements.
  
  
  METHODS
  Affymetrix Mouse Genome 430 2.0 oligonucleotide microarrays containing 45 102 probe sets were used to interrogate differential expression of genes in dietary-induced obesity model C57BL6 inbred mice fed a high-fat (35% fat; n=8) or standard (4% fat; n=6) diet from 3 to 15 wk of age. Ontologies of regulated genes were examined and expression of selected genes was validated by quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  One thousand two hundred twelve unique gene transcripts showed altered expression on the microarrays. Gene ontology analysis revealed changes in neuropeptide genes responding to leptin, Pomc, Cart, Npy, and Agrp, compatible with a homeostatic response to high-fat intake, although mean weight increased 2.3-fold compared with standard fed mice (P<0.001). Neurotransmitter system ontologies revealed upregulation of five genes controlling availability of dopamine. Changes in Th tyrosine hydroxylase (2.1-fold) and Slc18a2 solute carrier family 18 (vesicular monoamine), member 2 (4.4-fold) controlling synthesis and release, and Slc6a3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 (4.8-fold), Snca alpha-synuclein (1.3-fold), and Maoa monoamine oxidase (1.9-fold) limiting availability were confirmed by quantitative real-time polymerase chain reaction.
  
  
  CONCLUSIONS
  Expression of five genes involved in availability of dopamine was increased after a high-fat diet. Failure to reduce dopamine availability sufficiently, to counter the feeding reward effect, could contribute to diet-induced obesity in these mice.
authors.affiliation: Nutritional Sciences Division, King's College London, London, United Kingdom.
authors.forename: Alex K
authors.initials: AK
authors.lastname: Lee
authors.forename: Marjan
authors.initials: M
authors.lastname: Mojtahed-Jaberi
authors.forename: Theodosios
authors.initials: T
authors.lastname: Kyriakou
authors.forename: Estibaliz Aldecoa-Otalora
authors.initials: EA
authors.lastname: Astarloa
authors.forename: Matthew
authors.initials: M
authors.lastname: Arno
authors.forename: Nichola J
authors.initials: NJ
authors.lastname: Marshall
authors.forename: Susan D
authors.initials: SD
authors.lastname: Brain
authors.forename: Sandra D
authors.initials: SD
authors.lastname: O'Dell
mesh_terms: D000818:Animals; D004032:Diet / Q000379:methods*; D004041:Dietary Fats / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007031:Hypothalamus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D004041:Dietary Fats; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D004298:Dopamine