Associations Between Brain Gray Matter Volumes and Adipose Tissue Metabolism in Healthy Adults

Objective Gray matter (GM) volume in different brain loci has been shown to vary in obesity and diabetes, and elevated fasting plasma nonesterified fatty acid (NEFA) levels have been suggested as one potential mechanism. The hypothesis presented in this study is that brown adipose tissue (BAT) activity may correlate with GM volume in areas negatively associated with obesity and diabetes.Methods A total of 36 healthy patients (M/F: 12/24, age 39.7 +/- 9.4 years, BMI 27.5 +/- 5.6 kg/m(2)) were imaged with positron emission tomography using fatty acid analog [F-18]FTHA to measure NEFA uptake and with [O-15]H2O to measure perfusion during cold exposure, at room temperature during fasting, or during a postprandial state. A 2-hour hyperinsulinemic euglycemic clamp was performed to measure whole-body insulin sensitivity (M value, mean 7.6 +/- 3.9 mg/kg/min). T1-weighted magnetic resonance imaging at 1.5 T was performed on all patients.Results BAT NEFA uptake was associated directly with GM volume in anterior cerebellum and occipital lobe (P <= 0.04) when adjusted for age, gender, and intra-abdominal fat volume and with anterior cerebellum, limbic lobe, and temporal lobe GM volumes when adjusted for M value.Conclusions BAT NEFA metabolism may participate in protection from cognitive degeneration associated with cardiometabolic risk factors, such as central obesity and insulin resistance. Potential causal relationships between BAT activity and GM volumes remain to be examined

Changes in electrocardiogram parameters during acute nonshivering cold exposure and associations with brown adipose tissue activity, plasma catecholamine levels, and brachial blood pressure in healthy adults

Background: Sympathetic activity causes changes in electrocardiogram (ECG) during cold exposure and the changes have been studied mostly during hypothermia and less during mild acute nonshivering cold exposure. Cold-induced sympathetic activity also activates brown adipose tissue (BAT) and increases arterial blood pressure (BP) and plasma catecholamine levels. We examined changes in ECG parameters during acute nonshivering cold exposure and their associations with markers of sympathetic activity during cold exposure: brachial blood pressure (BP), plasma catecholamine levels, and BAT activity measured by positron emission tomography (PET).Methods and results: Healthy subjects (M/F = 13/24, aged 20-55 years) were imaged with [O-15]H2O (perfusion, N = 37) and [F-18]FTHA to measure plasma nonesterified fatty acid uptake (NEFA uptake, N = 37) during 2-h nonshivering cold exposure. 12-lead ECG (N = 37), plasma catecholamine levels (N = 17), and brachial BP (N = 31) were measured at rest in room temperature (RT) and re-measured after a 2-h nonshivering cold exposure. There were significant differences between RT and cold exposure in P axis (35.6 +/- 26.4 vs. 50.8 +/- 22.7 degrees, p = 0.005), PR interval (177.7 +/- 24.6 ms vs.163.0 +/- 28.7 ms, p = 0.001), QRS axis (42.1 +/- 31.3 vs. 56.9 +/- 24.1, p = 0.003), and QT (411.7 +/- 25.5 ms vs. 434.5 +/- 39.3 ms, p = 0.001). There was no significant change in HR, QRS duration, QTc, JTc, and T axis during cold exposure. Systolic BP (127.2 +/- 15.7 vs. 131.8 +/- 17.9 mmHg, p = 0.008), diastolic BP (81.7 +/- 12.0 vs. 85.4 +/- 13.0 mmHg, p = 0.02), and plasma noradrenaline level increased during cold exposure (1.97 +/- 0.61 vs. 5.07 +/- 1.32 mu mol/L, p = 0.001). Cold-induced changes in ECG parameters did not correlate with changes in BAT activity, brachial BP, plasma catecholamines, or skin temperature.Conclusions: During short-term nonshivering cold exposure, there were increases in P axis, PR interval, QRS axis, and QT compared to RT in healthy adults. Cold-induced changes in ECG parameters did not correlate with BAT activity, brachial BP, or plasma catecholamine levels which were used as markers of cold-induced sympathetic activity

Sex correction improves the accuracy of clinical dopamine transporter imaging

Background In clinical diagnostic imaging, dopamine transporter (DAT) SPECT scans are commonly evaluated using automated semiquantitative analysis software. Age correction is routinely implemented, but usually no sex correction of DAT binding is performed. Since there are sex differences in presynaptic dopaminergic function, we investigated the effect of DAT sex correction in a sample of healthy volunteers who underwent brain [I-123]-FP-CIT SPECT. Methods Forty healthy elderly individuals (21 men and 19 women) underwent brain [I-123]-FP-CIT SPECT, and each subject was examined clinically for motor and non-motor parkinsonian symptoms and signs. Regional specific DAT binding ratios (SBR = [ROI-occ]/occ) were calculated using age correction, and the results were compared to those in normal databases with and without sex correction. The level of regional abnormality was set at 2 standard deviations below the mean values of the reference databases. Results In the analysis without sex correction, compared to the mean ratio of the reference database, ten healthy individuals (8 men and 2 women) had abnormally low DAT binding ratios, and four individuals (3 men and 1 woman) had borderline low DAT binding ratios in at least one striatal region. When sex correction was implemented, the ratio of one individual was abnormal, and the ratio of one individual was borderline (both males). There were no clinically significant differences in motor or non-motor symptoms between healthy volunteers with abnormal and normal binding. Conclusions A considerable number of elderly healthy male subjects can be interpreted to be dopaminergically abnormal if no sex correction of DAT binding is performed. Sex differences in striatal dopaminergic function should be taken into account when DAT imaging is used to assist clinical diagnostics in patients with suspected neurological disorders.</p