Norepinephrine and T4 Are Predictors of Fat Mass Gain in Humans With Cold-Induced Brown Adipose Tissue Activation

Abstract

Context: In healthy adults with detectable cold-induced brown adipose tissue activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined.

Objective: To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes.

Design, setting, participants, and interventions: Twelve healthy volunteers (seven male and five female) with positive CIBA [>2 standardized uptake value (g/mL)] had 24-hour energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron emission tomography/computed tomography scans were performed after exposure to 16°C for 2 hours to quantify CIBA.

Main outcome measures: CIBA, 24hEE during EBL, and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 and free T4. Body composition at baseline and 6 months by dual-energy X-ray absorptiometry.

Results: Lower urinary norepinephrine and free T4 were associated with higher CIBA (r = -0.65, P = 0.03; and r = -0.75, P < 0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (P = 0.77). Lower CIBA (β = -3.5 kg/standardized uptake value; P < 0.01) predicted fat mass gain, whereas higher urinary norepinephrine and free T4 predicted future fat mass gain at 6 months (β = 3.0 kg per twofold difference in norepinephrine, P = 0.03; and β = 1.2 kg per 0.1-ng/dL difference in free T4, P = 0.03, respectively).

Conclusion: Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

Trial registration: ClinicalTrials.gov NCT00523627.

Figures

Figure 1.

Correlation of (A) BAT volume (g) and FM (kg), (B) correlation of CIBA mean SUV (g/mL) and FFM (kg), (C) 24hEE measured during EBL and thermoneutrality, after adjustment for FFM, and (D) 24-h mean RQ measured during EBL and thermoneutrality, after adjustment for body fat percentage.

Figure 2.

Correlation between (A) CIBA mean SUV (g/mL) and urinary norepinephrine (µg/24 h) measured during EBL and thermoneutrality and (B) urinary normetanephrine (µg/24 h) measured by HPLC during EBL and thermoneutrality. Relationship between free T4 (ng/dL) and both (C) CIBA and (D) BAT volume. Lack of correlation between plasma free T3 (pg/dL) and both (E) CIBA and (F) BAT volume. Both free T4 and free T3 were measured fasting the morning after EBL diet and during thermoneutrality. Results remained similar after serial adjustment for age, sex, FM, or FFM.

Figure 3.

Comparison of the 18F-FDG PET/CT images of the subjects with highest and lowest CIBA SUV values. Volunteer with the lowest urinary norepinephrine levels and lowest plasma free T4 images in the left panel, in which PET, CT, and fused coronal PET/CT images (A) show a large area of CIBA, with the highest SUV in our cohort of 4.57 SUV (g/mL).This series of images can be compared with the PET and CT and fused coronal PET/CT images (B) of the volunteer with the highest urinary norepinephrine and free T4 levels in the right panel, in which no visualization of CIBA is seen along with a mean SUV of 2.51 (g/mL), the lowest SUV in our cohort.

Figure 4.

Relationship between FM gain at 6 months and CIBA, urinary norepinephrine, free T4, and free T3. FM change was inversely associated with (A) CIBA and positively associated with both (B) 24-h urinary norepinephrine concentration and (C) free T4, whereas it was not associated with (D) free T3. Results by Pearson correlation coefficient.