Human brown adipose tissue [(15)O]O2 PET imaging in the presence and absence of cold stimulus

Eur J Nucl Med Mol Imaging. 2016 Sep;43(10):1878-86. doi: 10.1007/s00259-016-3364-y. Epub 2016 Mar 19.

Abstract

Purpose: 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.

Conclusion: 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.

Keywords: Brown adipose tissue; [15O]O2 PET imaging; cold-induced thermogenesis; oxygen consumption.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adipose Tissue, Brown / diagnostic imaging*
  • Adipose Tissue, Brown / physiology*
  • Adult
  • Cold Temperature
  • Cold-Shock Response / physiology*
  • Female
  • Humans
  • Male
  • Oxygen Consumption / physiology*
  • Oxygen Radioisotopes
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Thermogenesis / physiology*

Substances

  • Oxygen Radioisotopes
  • Radiopharmaceuticals