title: High expression of organic cation transporter 3 in human BAT-like adipocytes. Implications for extraneuronal norepinephrine uptake.
abstract: Brown adipose tissue (BAT) is activated by extracellular norepinephrine (NE) released by the sympathetic nervous system. The extracellular concentration of NE is additionally regulated by the disappearance/degradation of NE. Recent studies have introduced the organic cation transporter 3 (OCT3) as a possible contributor in the regulation of NE in adipose tissue. In the present study we set out to investigate the presence of OCT3 in human neck adipose tissue (AT), which is the primary localization of BAT in humans. Moreover, we wanted to assess the possible function and correlation of the transporter with known markers of thermogenic function, e.g. UCP1. When examining neck AT biopsies from 57 individuals we found that OCT3 was expressed at 2.5 ± 0.16 fold higher level in the deep-neck AT compared with subcutaneous AT. UCP1 was found extensively expressed in the deep-neck AT depot and the correlation between UCP1 and OCT3 within the deep-neck AT was found highly significant (r2= 0.4012, P-value < 0.0001). Lastly, we were able to reduce NE uptake in isolated brown adipocytes in an in vitro culture by adding corticosterone which is a known OCT3-blocker. In conclusion, we found that OCT3 may be a regulator of the concentration of NE in AT and by this mechanism a possible regulator of BAT function and a potential target for pharmacological intervention.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: peter.breining@clin.au.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Breining
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: steen.pedersen@clin.au.dk.
authors.forename: Steen Bønløkke
authors.initials: SB
authors.lastname: Pedersen
authors.affiliation: Department of Otorhinolaryngology, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: ARUNPI@rm.dk.
authors.forename: Arunas
authors.initials: A
authors.lastname: Pikelis
authors.affiliation: Department of Otorhinolaryngology, Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Surgery P, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: larsroli@rm.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Rolighed
authors.affiliation: Research Laboratory for Biochemical Pathology, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: elias.sundelin@clin.au.dk.
authors.forename: Elias Immanuel Ordell
authors.initials: EIO
authors.lastname: Sundelin
authors.affiliation: Research Laboratory for Biochemical Pathology, Aarhus University Hospital, 8000 Aarhus C, Denmark; Department of Clinical Pharmacology, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: niels.jessen@clin.au.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus C, Denmark. Electronic address: bjoern.richelsen@aarhus.rm.dk.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Richelsen
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015992:Body Mass Index; D002469:Cell Separation; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009333:Neck; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D022722:Thermogenesis / Q000235:genetics; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D029362:Organic Anion Transporters, Sodium-Independent; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; C114338:organic anion transport protein 3; D009638:Norepinephrine
keywords: Brown adipose tissue; Norepinephrine; Organic cation transporter 3; Thermogenesis; Uncoupling protein 1