People with brown fat burned significantly more calories in response to cold than those without -- another finding that supports the tissue's potential as a target for weight loss, scientists said.
After a 90-minute bout of exposure to cold, eight volunteers with brown fat burned 15% more calories, or an extra 20 kilocalories per day, than age- and weight-matched volunteers without brown fat, reported Florian Kiefer, MD, PhD, of the Medical University of Vienna, and colleagues.
As shown in the team's study online in the , the volunteers with brown fat also had a unique polyunsaturated fatty acid (PUFA) and oxylipin profile with potentially anti-inflammatory and metabolically favorable characteristics. In addition, those with brown fat had higher circulating levels of various lipids, including the brown fat-derived lipokines diHOME and 12-HEPE, in response to cold.
These findings add to the growing body of evidence that brown fat is involved in metabolic processes beyond thermogenesis, including lipid metabolism and inflammation, the researchers said.
"Despite accumulating evidence that BAT [brown adipose tissue] activation is associated with increased energy expenditure, improved insulin sensitivity, and lipid clearance in humans, direct comparison of substrate metabolism and lipid species in matched individuals with and without active BAT depots have not been studied yet," the team wrote. "We found that a single bout of cold exposure significantly elevated energy expenditure for more than 2 hours after cessation of the cold challenge whereas cold-induced energy expenditure was absent in BAT-negative individuals."
Furthermore, "the presence of active BAT was associated with an anti-inflammatory oxylipin/eicosanoid profile, and cold exposure increased systemic oxylipin levels only in BAT-positive but not BAT-negative subjects," Kiefer and co-authors continued. "The fact that very distinct lipid clusters are regulated concomitantly by BAT status and cold exposure strongly suggests that BAT is indeed an important organ orchestrating the systemic PUFA/oxylipin pool in a coordinated manner and therefore warrants further investigation."
The study included 16 healthy volunteers matched by age and body mass index (BMI) who had been previously identified as BAT-positive or -negative in a cross-sectional imaging study. There were eight participants in each group, all of whom underwent an initial positron emission tomography/computed tomography (PET/CT) scan at room temperature (23°C) to detect any basal BAT activity. After that, the participants underwent indirect calorimetry examinations before, during, and after 90 minutes of cold exposure to assess the magnitude and duration of cold-induced energy expenditure.
The cold challenge was done with a water-perfused cooling vest, with the water kept slightly above the shivering temperature. After the challenge, as participants warmed up, indirect calorimetry measurements were repeated every hour until energy expenditure returned to baseline levels. Blood was taken before and after the cold exposure for laboratory analysis.
Kiefer told that the results suggest the possibility, although still speculative, that cold exposure could one day be used for weight loss. "Such interventions could include repeated moderate cold-exposure -- e.g., by using cooling vests, although this might not be very practical in daily life," he said via email. "Some studies are already looking into potential pharmacological interventions that may activate and/or recruit BAT. One such agent is the beta-3 receptor agonist mirabegron [Myrbetriq], a medication that is currently approved for the treatment of overactive bladder."
A limitation of the study, the researchers said, was its small sample size, due to the age- and BMI-matched design, as well as the expensive technology used. "Also, the radioactive exposure associated with [18F]-FDG PET/CT scans would hardly justify the screening of a larger number of subjects given that these were healthy volunteers. Despite the small sample size and the exploratory nature of the study, we found a robust regulation of several lipid species by cold exposure and BAT status which is in accordance with previous reports of cold-induced BAT-derived oxylipins," the investigators noted, adding that it is possible that other tissues responsive to cold stimulation contributed to the study's findings.
Kiefer said his group is continuing to study brown fat. "We are currently studying metabolic differences between lean and obese subjects with or without active BAT to better understand the relevance of brown fat in metabolic disease," he said. "Other research is dedicated to identifying novel BAT-secreted signaling molecules that may also serve as potential biomarkers of BAT function."
Disclosures
The study was supported by the Vienna Science and Technology Fund, the Austrian Science Fund, and the Austrian Diabetes Association Research Fund.
Kiefer and co-authors reported having no conflicts of interest.
Primary Source
Journal of Clinical Endocrinology & Metabolism
Kulterer OC, et al "The presence of active brown adipose tissue determines cold-induced energy expenditure and oxylipin profiles in humans" J Clin Endocrinol Metab 2020; DOI: 10.1210/clinem/dgaa183.