Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls

Figures & data

Table 1. Subject characteristics and dex/CRH test indicators.

	Non-obesity controls	Obesity group	p-Value
Number of subjects	10	10
Sex, male/female	6/4	6/4	1.0b
Age (years)	33.3 ± 10.0	34.4 ± 9.0	0.80a
Body mass index (kg/m^2)	23.9 ± 2.5 (21.7 - 28.7)	42.4 ± 3.7 (35.7 - 47.8)	<0.0001 a
Waist circumference (cm)	89.3 ± 6.3	128.9 ± 13.4	<0.0001 a
Waist/Hip ratio	0.91 ± 0.1	0.96 ± 0.09	0.27a
Ethnicity	Caucasian
ACTHMAX	2.69 (1.89–4.30)	1.86 (1.34–6.28)	0.47c
ACTHAUC	7.85 (5.44–14.05)	6.26 (4.32–18.82)	0.76c
CortisolMAX	77.8 (36.6–193.4)	123.2 (29.0–284.7)	0.71c
CortisolAUC	226.1 (85.4–552.2)	378.2 (97.8–918.5)	0.55c
ACTH/CortisolMAX	0.037 (0.023–0.051)	0.022 (0.017–0.046)	0.17c
ACTH/CortisolAUC	0.035 (0.027–0.055)	0.023 (0.016–0.044)	0.13c
Copeptinpost-dex	3.10 (2.01–4.15)	4.32 (2.10–6.54)	0.41c
Osmolality (mosmol/kg)	293.9 ± 4.6	290.8 ± 6.6	0.33a
Sodium (mmol/l)	140.8 ± 2.6	139.5 ± 3.1	0.60a

^a t-test;

^bPearson's Chi-Square test;

^cMann–Whitney U-test. Data are given as mean ± standard deviation (range) or median (interquartile range). BMI: body mass index. Bold: significant at p < .05.

Figure 1. Regions-of-interest for the quantification of noradrenaline transporter availability. The outlined regions-of-interest are exemplarily shown on an individual MR (top row). The same regions are depicted with arrows on an averaged parametric PET (NAT DVR) image (bottom row).

Figure 2. HPA responsiveness in the course of time. Obesity group vs. non-obesity controls. Time course of ACTH (A) and cortisol response (B) to the combined dex/CRH test in subjects with obesity (N = 10; solid line, squares) and non-obesity controls (N = 10; dashed line, circles). After 1.5 mg dexamethasone, taken orally at 2300 h, the night before the test, a bolus of 100 ug CRH was applied i.v. at 1502 h. Data are given as mean with standard error. Dex: dexamethasone; CRH: corticotropin-releasing hormone; ACTH: adrenocorticotropic hormone.

Figure 3. Non-obesity controls. NAT DVR in relation to HPA axis responsiveness and serum copeptin. Noradrenaline transporter distribution volume ratios and neuroendocrine parameters in non-obesity controls. Spearman-rho and p-value given for significant correlations. Data are presented in ranks with regression line and 95% confidence interval. MAX: maximum; ACTH: adrenocorticotropic hormone. Significant positive correlations were found between noradrenaline transporter (NAT) distribution volume ratios (DVR) of the orbitofrontal cortex (OFC) and the amygdala with ACTH and cortisol maxima (D, E, G, H). No correlation of copeptin with NAT DVR was found (C, F, I).

Figure 4. Obesity group. NAT DVR in relation to HPA responsiveness and serum copeptin. Noradrenaline transporter distribution volume ratios and neuroendocrine parameters in the obesity group. Spearman-rho and p-value given for significant correlations. Data are presented as ranks with regression line and 95% confidence interval. MAX: maximum; ACTH: adrenocorticotropic hormone. Significant negative correlations were found between noradrenaline transporter (NAT) distribution volume rations (DVR) of the hypothalamus with cortisol maximum (B) and copeptin, measured after dexamethasone ingestion, prior to CRH administration (C). No correlations between the neuroendocrine parameters with NAT DVR of the orbitofrontal cortex (OFC) or amygdala DVR were found (D–I).

Table 2. Spearman correlation of dex/CRH test indicators and noradrenaline transporter availability.

	Obesity group					Non-obesity controls
	ACTHMAX	ACTHAUC	CortisolMAX	CortisolAUC	Copeptin	ACTHMAX	ACTHAUC	CortisolMAX	CortisolAUC	Copeptin
OFC	0.21 (0.56)	0.21 (0.56)	0.05 (0.88)	0.05 (0.88)	−0.35 (0.33)	0.87 (0.001)	0.86 (0.002)	0.86 (0.002)	0.84 (0.002)	−0.24 (0.51)
Insula	−0.22 (0.53)	−0.22 (0.53)	−0.21 (0.56)	−0.21 (0.56)	−0.44 (0.21)	0.32 (0.37)	0.18 (0.63)	0.38 (0.28)	0.24 (0.51)	−0.21 (0.56)
Hippocampus	−0.30 (0.40)	−0.30 (0.40)	−0.44 (0.20)	−0.44 (0.20)	−0.65 (0.04)	0.16 (0.65)	0.14 (0.70)	0.12 (0.75)	0.10 (0.78)	0.30 (0.41)
Amygdala	−0.01 (0.99)	−0.01 (0.99)	−0.07 (0.85)	−0.07 (0.85)	−0.05 (0.89)	0.86 (0.002)	0.88 (0.001)	0.79 (0.006)	0.75 (0.013)	0.08 (0.83)
Thalamus	−0.50 (0.14)	−0.50 (0.14)	−0.15 (0.68)	−0.15 (0.68)	−0.35 (0.33)	0.13 (0.73)	0.03 (0.93)	−0.01 (0.99)	0.10 (0.78)	−0.27 (0.45)
Hypothalamus	−0.50 (0.14)	−0.50 (0.14)	−0.66 (0.04)	−0.66 (0.04)	−0.71 (0.02)	0.14 (0.70)	−0.02 (0.96)	0.09 (0.80)	−0.01 (0.99)	0.04 (0.91)
Locus coeruleus	0.16 (0.65)	0.16 (0.65)	−0.19 (0.60)	−0.19 (0.60)	0.24 (0.51)	0.31 (0.38)	0.15 (0.68)	0.30 (0.40)	0.24 (0.51)	−0.10 (0.78)

Spearman-rho coefficients and significance values (p). MAX: maximum; AUC: area under the curve; ACTH: adrenocorticotropic hormone; OFC: orbito-frontal cortex. ACTH in pmol/l, cortisol in nmol/l, AUC expressed as arbitrary unit. Noradrenaline transporter availability was indexed by distribution volume ratios. Bold: significant at p < .05.