title: Human brown adipose tissue [(15)O]O2 PET imaging in the presence and absence of cold stimulus.
abstract: OBJECTIVE
  Brown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [(15)O]O2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE.
  
  
  METHODS
  Seven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [(15)O]O2, [(15)O]H2O, and [(18)F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold.
  
  
  RESULTS
  BAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2-47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus.
  
  
  CONCLUSIONS
  Our study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake.
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Mueez
authors.initials: M
authors.lastname: U Din
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Juho
authors.initials: J
authors.lastname: Raiko
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Saari
authors.affiliation: Department of Medical Physics, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Nobu
authors.initials: N
authors.lastname: Kudomi
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Tuula
authors.initials: T
authors.lastname: Tolvanen
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Teuho
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Hannu T
authors.initials: HT
authors.lastname: Sipilä
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Savisto
authors.affiliation: Department of Radiology, Turku University Hospital and University of Turku, Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Parkkola
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.affiliation: Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520, Turku, Finland. kirsi.virtanen@utu.fi.|Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520, Turku, Finland. kirsi.virtanen@utu.fi.
authors.forename: Kirsi A
authors.initials: KA
authors.lastname: Virtanen
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging* / Q000502:physiology*; D000328:Adult; D003080:Cold Temperature; D058639:Cold-Shock Response / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D010104:Oxygen Radioisotopes; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D022722:Thermogenesis / Q000502:physiology*
chemical_list: D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals
keywords: Brown adipose tissue; [15O]O2 PET imaging; cold-induced thermogenesis; oxygen consumption