Norepinephrine transporter availability in brown fat is reduced in obesity: a human PET study with [11C] MRB

Int J Obes (Lond). 2020 Apr;44(4):964-967. doi: 10.1038/s41366-019-0471-4. Epub 2019 Oct 21.

Abstract

The energy-dissipating properties of brown adipose tissue (BAT) have been proposed as therapeutic targets for obesity and diabetes. Little is known about basal BAT activity. Capitalizing on the dense sympathetic innervation of BAT, we have previously shown that BAT can be detected in humans under resting room temperature (RT) conditions by using (S,S)-11C-O-methylreboxetine (MRB), a selective ligand for the norepinephrine transporter (NET). In this study, we determine whether MRB labeling of human BAT is altered by obesity. Fifteen healthy, nondiabetic Caucasian women (nine lean, age 25.6 ± 1.7, BMI 21.8 ± 1.3 kg/m2; six obese age 30.8 ± 8.8 BMI 37.9 ± 6.6 kg/m2) underwent PET-CT imaging of the neck/supraclavicular region using 11C-MRB under RT conditions. The distribution volume ratio (DVR) for 11C-MRB was estimated via multilinear reference tissue model 2 (MRTM2) referenced to the occipital cortex. Two women (one lean and one with obesity) had no detectable BAT. Of the women with detectable BAT, women with obesity had lower 11C-MRB DVR (0.80 ± 0.12 BAT DVR) compared to lean (1.15 ± 0.19 BAT DVR) (p = 0.004). Our findings are consistent with reports that NET is decreased in obesity and suggest that the sympathetic innervation of BAT is altered in obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown* / diagnostic imaging
  • Adipose Tissue, Brown* / metabolism
  • Adult
  • Carbon Radioisotopes / pharmacokinetics
  • Female
  • Humans
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism*
  • Obesity* / diagnostic imaging
  • Obesity* / metabolism
  • Positron Emission Tomography Computed Tomography
  • Reboxetine / pharmacokinetics
  • Young Adult

Substances

  • Carbon Radioisotopes
  • Norepinephrine Plasma Membrane Transport Proteins
  • O-methyl reboxetine
  • SLC6A2 protein, human
  • Reboxetine