Sympathetic Innervation of Cold-Activated Brown and White Fat in Lean Young Adults

Abstract

Recent work in rodents has demonstrated that basal activity of the local sympathetic nervous system is critical for maintaining brown adipocyte phenotypes in classic brown adipose tissue (BAT) and white adipose tissue (WAT). Accordingly, we sought to assess the relationship between sympathetic innervation and cold-induced activation of BAT and WAT in lean young adults. Methods: Twenty adult lean normal subjects (10 women and 10 men; mean age 6 SD, 23.3 6 3.8 y; body mass index, 23.7 6 2.5 kg/m 2 ) underwent 11 C-meta-hydroxyephedrin ( 11 C-HED) and 15 O-water PET imaging at rest and after exposure to mild cold (16°C) temperature. In addition, 18 F-FDG images were obtained during the cold stress condition to assess cold-activated BAT mass. Subjects were divided into 2 groups (high BAT and low BAT) based on the presence of 18 F-FDG tracer uptake. Blood flow and 11 C-HED retention index (RI, an indirect measure of sympathetic innervation) were calculated from dynamic PET scans at the location of BAT and WAT. Whole-body daily energy expenditure (DEE) during rest and cold stress was measured by indirect calorimetry. Tissue level oxygen consumption (MRO 2 ) was determined and used to calculate the contribution of cold-activated BAT and WAT to daily DEE. Results: 18 F-FDG uptake identified subjects with high and low levels of cold-activated BAT mass (high BAT, 96 6 37 g; low-BAT, 16 6 4 g). 11 C-HED RI under thermoneutral conditions significantly predicted 18 F-FDG uptake during cold stress (R 2 5 0.68, P , 0.01). In contrast to the significant increase of 11 C-HED RI during cold in BAT (2.42 6 0.85 vs. 3.43 6 0.93, P 5 0.02), cold exposure decreased the 11 C-HED RI in WAT (0.44 6 0.22 vs. 0.41 6 0.18) as a consequence of decreased perfusion (1.22 6 0.20 vs. 1.12 6 0.16 mL/100 g/min). The contribution of WAT to whole-body DEE was approximately 150 kcal/d at rest (149 6 52 kcal/d), which decreased to approximately 100 kcal/d during cold (102 6 47 kcal/d). Conclusion: The level of sympathetic innervation, as determined by 11 C-HED RI, can predict levels of functional BAT. Overall, blood flow is the best independent predictor of 11 C-HED RI and 18 F-FDG uptake across thermoneutral and cold conditions. In contrast to BAT, cold stress reduces blood flow and 18 F-FDG uptake in subcutaneous WAT, indicating that the physiologic response is to reduce heat loss rather than to generate heat.

Brown adipose tissue, energy expenditure, and biomarkers of cardio‐metabolic health among the Yakut (Sakha) of northeastern Siberia

“…In contrast, the change in skin temperature of a point on the sternum, which lacks BAT deposits, was negatively associated with change in energy expenditure. The positive relationship between ΔSCV and energy expenditure during cold exposure is consistent with previous investigations (Chen et al, ; Muzik et al, ; van der Lans et al, ; van Marken Licthenbelt et al, ; Yoneshiro et al, ). Interestingly, participants who experienced an increase in SCV temperature had a mean % ΔEE of +1.41%, while participants who experienced a decrease in SCV temperature had a mean % ΔEE of −6.49%.…”

“…The study detected a significant increase in RQ after cooling in women but not men (see Tables and ). A similar pattern was detected by Hadi et al () after immersing subjects' hands in 5°C water for 20 minute; however, most investigations of NST report no change in RQ (Celi et al, ; Hanssen et al, ; Muzik et al, ; Peterson et al, ; Stelly, ; U Din et al, ). An increase in RQ among women may represent a shift toward utilizing carbohydrates as a metabolic substrate for thermogenesis.…”

The Mediating Role of Brown Fat and Skeletal Muscle Measured by 18F‐Fluorodeoxyglucose in the Thermoregulatory System in Young Adults

“…Several studies have shown that human BAT activation is related to an increase in the blood flow in BAT . Based on these results, the present study postulates that the increase in BAT activation (blood flow) could result in a redistribution of the blood in the peripheral part of the body during a cold stimulus in order to generate heat, as BAT is highly irrigated .…”

Neuronal Modulation of Brown Adipose Activity Through Perturbation of White Adipocyte Lipogenesis

“…1). Other studies have demonstrated increased activity of sympathetic nerves in iWAT and BAT after cold stimulus 34,35 and upon central nervous system activation such as direct administration of FGF21 peptide in the brain 36 or via local optogenetic activation of sympathetic fibers 37 . The idea that communication occurs between WAT and BAT in both directions has also been previously described.…”