title: Dopaminergic Receptors and Tyrosine Hydroxylase Expression in Peripheral Blood Mononuclear Cells: A Distinct Pattern in Central Obesity.
abstract: BACKGROUND
  Dopamine (DA) may be involved in central obesity (CO), an inflammatory condition, through its role in the central nervous system and in periphery, where it may affect immune cell function through five different DA receptors (DR). Whether dopaminergic pathways in peripheral immune cells are implicated in the inflammatory condition linked to CO is however unknown.
  
  
  METHODS
  In a cohort of blood donors with and without CO, categorized by waist circumference (WC) (CO: WC ≥ 0.80 m in women and ≥ 0.94 m in men), we studied the expression of DR and tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of DA, in peripheral blood mononuclear cells (PBMCs) and their relation with anthropometric and metabolic/endocrine and inflammatory parameters. DR D1-5 and TH expression was assessed by semi quantitative real-time PCR. As inflammatory markers we investigated the immunophenotype of monocyte subsets by flow cytometry, staining for CD14, CD16, CD11b and CD36.
  
  
  RESULTS
  CO individuals showed higher plasma levels of leptin and higher inflammatory pattern of monocytes compared with non-CO. PBMC expression of DR D2, DR D4 and DR D5 as well as of TH were lower in CO in comparison with non-CO. DR D2, and DR D5 expression correlated with lower WC and weight, and with lower inflammatory pattern of monocytes, and TH expression correlated with lower WC. DR D4 expression correlated with lower plasma levels of glycosylated hemoglobin, and DR D2 expression correlated with lower CO.
  
  
  CONCLUSIONS
  Results show that CO is associated with peripheral inflammation and downregulation of dopaminergic pathways in PBMCs, possibly suggesting DR expressed on immune cells as pharmacological targets in obesity for better metabolic outcome.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal.|Department of Clinical Haematology, Centro Hospitalar of Porto, Porto, Portugal.|Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto- UMIB/ICBAS/UP, Porto, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Leite
authors.affiliation: Department of Clinical Haematology, Centro Hospitalar of Porto, Porto, Portugal.|Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto- UMIB/ICBAS/UP, Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
authors.affiliation: Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.affiliation: Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal.|Department of Medical Education and Simulation, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Laura
authors.initials: L
authors.lastname: Ribeiro
mesh_terms: D000328:Adult; D000886:Anthropometry; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000097:blood* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D011954:Receptors, Dopamine / Q000097:blood* / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D014446:Tyrosine 3-Monooxygenase