Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature

Abstract

Context: The contribution of brown adipose tissue (BAT) to the energy balance in humans exposed to sustainable cold has not been completely established, partially because of measurement limitations of both BAT activity and energy expenditure (EE).

Objective: The objective of the study was to characterize the role of BAT activation in cold-induced thermogenesis (CIT).

Design: This study was a single-blind, randomized crossover intervention.

Setting: The study was conducted at the National Institutes of Health Clinical Center.

Study participants: Thirty-one healthy volunteers participated in the study.

Interventions: The intervention included mild cold exposure.

Main outcomes: CIT and BAT activation were the main outcomes in this study.

Methods: Overnight EE measurement by whole-room indirect calorimeter at 24 °C or 19 °C was followed by 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan. After 36 hours, volunteers crossed over to the alternate study temperature under identical conditions. BAT activity was measured in a 3-dimensional region of interest in the upper torso by comparing the uptake at the two temperatures.

Results: Twenty-four volunteers (14 males, 10 females) had a complete data set. When compared with 24 °C, exposure at 19 °C resulted in increased EE (5.3 ± 5.9%, P < .001), indicating CIT response and mean BAT activity (10.5 ± 11.1%, P < .001). Multiple regression analysis indicated that a difference in BAT activity (P < .001), age (P = .01), and gender (P = .037) were independent contributors to individual variability of CIT.

Conclusions: A small reduction in ambient temperature, within the range of climate-controlled buildings, is sufficient to increase human BAT activity, which correlates with individual CIT response. This study uncovers for the first time a spectrum of BAT activation among healthy adults during mild cold exposure not previously recognized by conventional PET and PET-computed tomography methods. The enhancement of cold-induced BAT stimulation may represent a novel environmental strategy in obesity treatment.

Figure 1.

Analysis of PET images using the torso-mantle method demonstrating ¹⁸F-FDG uptake in BAT depots located in the cervical-supraclavicular-thoracic region during exposure to 19°C in a 26-year-old man (A). No FDG uptake was visible when the scan was performed at 24°C (B). Correlations between BAT uptake, age, and cold-induced thermogenesis are shown. C, Correlation between cold-induced thermogenesis (expressed as the difference in EE between 19°C and 24°C) and BAT activation (SUV). D, Correlation between cold-induced thermogenesis and age. Square symbols, females; round symbols, males; filled symbols, BAT positive; empty symbols, BAT negative. Bottom, Stepwise regression analysis for independent contribution to cold-induced thermogenesis.