Brown adipose tissue influences adiponectin and thyroid hormone changes during Graves’ disease therapy

Figures & data

Figure 1. Study protocol.

Table 1. Clinical and anthropometric patient data and summary of treatment outcomes.

Clinical and anthropometric parameters (n = 21)
Parameter	Hyperthyroid	Euthyroid	P-value
	Mean ± SEM	Mean ± SEM
Weight (kg)	55.6 ± 2.6	58.5 ± 2.9	0.001
BMI (kg/m^2)	21.7 ± 0.9	22.9 ± 1.1	0.001
Fat mass (kg)	19.5 ± 1.6	20.3 ± 1.7	0.040
Lean mass (kg)	33.8 ± 1.6	35.7 ± 1.8	<0.001
Waist circumference (cm)	77.5 ± 2.7	80.4 ± 2.6	0.055
Mean SUV (g/mL)	0.9 ± 0.1	0.8 ± 0.1	0.926
Max SUV (g/mL)	1.7 ± 0.2	1.9 ± 0.2	0.518
sFF mean (%)	72.3 ± 1.4	76.8 ± 1.4	<0.001
Free T4 (pmol/L)	29.9 ± 3.0	12.3 ± 1.3	<0.001
Free T3 (pmol/L)	10.5 ± 0.9	5.5 ± 0.3	<0.001
Glucose (mmol/L)	4.4 ± 0.1	4.5 ± 0.1	0.714
Albumin (g/L)	40.2 ± 0.6	43.4 ± 0.5	<0.001
Cholesterol (mmol/L)	4.6 ± 0.2	5.6 ± 0.3	<0.001
Triglyceride (mmol/L)	1.4 ± 0.2	1.2 ± 0.2	0.060
HDL-C (mmol/L)	1.4 ± 0.1	1.7 ± 0.1	<0.001
LDL-C (mmol/L)	2.6 ± 0.2	3.3 ± 0.2	0.001
Insulin (mU/L)	5.4 ± 0.7	6.1 ± 0.8	0.330
HOMA-IR score	1.1 ± 0.1	1.2 ± 0.2	0.388
RMR (kcal/d)	1718.6 ± 87.7	1430.2 ± 65.2	<0.001
SAT (cm^3)	54.7 ± 5.9	53.9 ± 5.6	0.210
VAT (cm^3)	22.9 ± 2.9	22.6 ± 3.1	0.681
DSAT (cm^3)	31.8 ± 4.2	30.2 ± 4.0	0.898
SSAT (cm^3)	22.9 ± 1.8	23.7 ± 1.7	0.007
Adiponectin (ng/mL)	5981.0 ± 832.1	7800.7 ± 793.6	0.001

Data presented as means ± SEM. P-values represent paired t-tests between patient measurements at baseline hyperthyroid state and achievement of euthyroidism after treatment.

Figure 2. Significant Pearson correlations between Δ adiponectin (ng/mL) and (a) Δ FT4, (b) Δ serum cholesterol, (c) Δ HDL-C, (d) Δ LDL-C following correction of hyperthyroidism. These markers thus serve as good predictors for serum adiponectin changes during the correction of hyperthyroidism in patients with Graves’ disease.

Figure 2. (continued).

Table 2. Significant differences in measured variables and adiponectin measurements between BAT-positive and BAT-negative patients.

Parameter	BAT-positive (n = 8)	BAT-negative (n = 13)	P-value
	Mean ± SEM	Mean ± SEM
Mean SUV HT (g/mL)	1.2 ± 0.1	0.7 ± 0.1	0.011
Max SUV HT (g/mL)	2.4 ± 0.3	1.3 ± 0.1	0.014
sFF mean HT (%)	68.1 ± 1.5	74.9 ± 1.8	0.010
Glucose HT (mmol/L)	4.7 ± 0.1	4.2 ± 0.1	0.042
Cholesterol HT (mmol/L)	4.0 ± 0.3	5.0 ± 0.3	0.045
LDL-C HT (mmol/L)	2.1 ± 0.2	2.9 ± 0.3	0.049
Free T4 HT (pmol/L)	37.9 ± 4.6	25.0 ± 3.3	0.038
sFF mean ET (%)	72.7 ± 1.1	79.3 ± 1.9	0.007
Triglyceride ET (mmol/L)	0.7 ± 0.1	1.5 ± 0.3	0.008
Insulin ET (mU/L)	4.3 ± 0.7	7.3 ± 1.2	0.040
HOMA-IR ET	0.8 ± 0.1	1.5 ± 0.2	0.037
Free T4 ET (pmol/L)	−25.1 ± 3.9	−13.0 ± 2.6	0.023
Adiponectin HT (ng/mL)	7211.2 ± 1441.5	5223.9 ± 996.4	0.277
Adiponectin ET (ng/mL)	9410.5 ± 1290.0	6810.1 ± 940.0	0.125
Δ Adiponectin (ng/mL)	2199.4 ± 957.9	1586.2 ± 516.9	0.584

Data presented as mean ± SEM. P values represents Student’s t-test done to identify differences in variables based on BAT status. Highlighted cells point out the absence of any significant difference in adiponectin measurements between the groups.

Figure 3. Representative 18 F-FDG PET images illustrating tracer uptake and standardized uptake values (SUV) within the circumscribed regions of interest (ROI) correlating to supraclavicular brown adipose tissue (sBAT) depots. There is higher tracer uptake and SUV in a (a) BAT-positive hyperthyroid patient and a correspondingly lower uptake and SUV within the same ROI in a (b) BAT-negative hyperthyroid patient.

Table 3. Differences in treatment outcomes of BAT-positive and BAT-negative patients.

Parameter	BAT-positive (n = 8)			BAT-negative (n = 13)
	Hyperthyroid	Euthyroid	P-value	Hyperthyroid	Euthyroid	P-value
	Mean ± SEM	Mean ± SEM		Mean ± SEM	Mean ± SEM
sFF mean (kg)	68.1 ± 1.3	72.7 ± 1.1	0.011	74.9 ± 1.8	79.3 ± 1.9	<0.001
Weight (kg)	52.4 ± 3.3	53.9 ± 3.6	0.088	57.6 ± 3.5	61.4 ± 4.1	0.004
BMI (kg/m^2)	20.5 ± 0.8	21.1 ± 0.8	0.100	22.4 ± 1.3	24.0 ± 1.6	0.003
Fat mass (kg)	17.2 ± 1.5	17.3 ± 1.7	0.772	20.9 ± 2.4	22.2 ± 2.4	0.036
Lean mass (kg)	32.9 ± 2.4	34.1 ± 2.5	0.123	34.3 ± 2.0	36.7 ± 2.6	0.002
Cholesterol (mmol/L)	4.0 ± 0.3	4.9 ± 0.4	0.061	5.0 ± 0.3	6.0 ± 0.4	0.002
HDL-C (mmol/L)	1.4 ± 0.1	1.7 ± 0.2	0.074	1.4 ± 0.1	1.7 ± 0.1	0.001
LDL (mmol/L)	2.1 ± 0.2	2.9 ± 0.3	0.045	2.9 ± 0.3	3.6 ± 0.3	0.009
FT4 (pmol/L)	37.9 ± 4.1	12.8 ± 1.7	<0.001	25.0 ± 3.3	11.9 ± 1.9	<0.001
FT3 (pmol/L)	13.0 ± 1.5	5.9 ± 0.6	0.002	8.9 ± 0.9	5.2 ± 0.3	<0.001
RMR (kcal/d)	1839.0 ± 150.4	1493.7 ± 150.5	0.006	1644.5 ± 95.2	1391.1 ± 54.7	<0.001
SSAT (cm^3)	21.3 ± 2.1	22.0 ± 2.2	0.228	22.9 ± 2.5	24.8 ± 2.5	0.018
Adiponectin (ng/mL)	7211.2 ± 1271.3	9410.5 ± 1290.0	0.055	5223.9 ± 996.4	6810.1 ± 940.0	0.010

Values are presented as mean ± SEM. P-values represent paired t-tests between BAT-positive and BAT-negative patient measurements at baseline hyperthyroid state and achievement of euthyroidism after treatment respectively. Highlighted cells point out differences in post-treatment outcomes between BAT subgroups.

Figure 4. Differences in adiponectin levels in hyperthyroid and euthyroid states in both BAT-positive and BAT-negative groups.

Table 4. Loss of FT4 association with adiponectin in BAT-positive patients.

Parameter	Overall (n = 21)		BAT-positive (n = 8)		BAT-negative (n = 13)
	Δ Adiponectin (ng/mL)		Δ Adiponectin (ng/mL)		Δ Adiponectin (ng/mL)
	Coefficient	P-value	Coefficient	P-value	Coefficient	P-value
Δ Albumin (mmol/L)	0.633	0.002	0.74	0.036	0.633	0.02
Δ Cholesterol (mmol/L)	0.719	<0.001	0.781	0.022	0.684	0.01
Δ HDL-C (mmol/L)	0.668	<0.001	0.71	0.049	0.672	0.012
Δ LDL-C (mmol/L)	0.639	0.002	0.778	0.023	0.516	0.071
Δ HOMA-IR score	−0.409	0.066	−0.305	0.462	−0.484	0.094
Δ Free T4 (pmol/L)	−0.562	0.008	−0.517	0.189	−0.648	0.017

Pearson Correlations were used to assess relationships between variables. Highlighted cells point out differences in correlations between BAT subgroups.

Figure 5. Changes in mean HOMA-IR scores between hyperthyroid and euthyroid states of the overall sample, BAT-positive and BAT-negative subjects.

Table

Δ	changes from treatment
18 F-FDG	18 F-fluorodeoxyglucose
ATD	anti-thyroid drug
BAT	brown adipose tissue
BMI	body mass index
DBP	diastolic blood pressure
DSAT	deep subcutaneous adipose tissue
DXA	dual-energy X-ray absorptiometry
ET	euthyroid
FOX	fatty acid oxidation
FT3	free T3 (triiodothyronine)
FT4	free T4 (tetraiodothyronine or thyroxine)
HDL	high-density lipoprotein
HOMA-IR	homoeostatic model assessment for insulin resistance
HT	hyperthyroid
IRT	infrared thermography
LDL	low-density lipoprotein
MR	magnetic resonance
NEFA	non-esterified fatty acids
PET	positron-emission tomography
PPAR-α	peroxisome proliferator-activated receptor-α
RMR	resting metabolic rate
SAT	subcutaneous adipose tissue
sBAT	supraclavicular brown adipose tissue
SBP	systolic blood pressure
SEM	standard error of mean
sFF	supraclavicular fat fraction
SSAT	superficial subcutaneous adipose tissue
SUV	standardized uptake value
VAT	visceral adipose tissue
WAT	white adipose tissue
WBC	whole body calorimetry