Brown Adipose Tissue in Morbidly Obese Subjects

BACKGROUND: Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. METHODS AND FINDINGS: After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans. CONCLUSIONS: This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity

Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET

F-18-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent F-18-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average F-18-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. F-18-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. F-18-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that F-18-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course

PET-images of fifteen morbidly obese subjects.

<p>Three female subjects showed BAT activity in the supraclavicular area, highlighted by a red rectangle (A). Combined PET- and CT-imaging shows FDG-uptake in supraclavicular adipose tissue (this was the morbidly obese subject that showed the most BAT activity) (B).</p

Brown adipose tissue activity in relation to body mass index (A) and body fat percentage (B).

<p>The black dots indicate the current study group, the open dots indicate previously performed measurements. Cold-induced thermogenesis (CIT), denoted in percentages, is significantly increased in 26 BAT-positive (BAT+) compared to 13 BAT-negative (BAT-) subjects (C). *: P<0.05.</p

Energy expenditure, body core temperature, mean skin temperature and core-skin temperature gradient in thermoneutral conditions (TN) and during mild cold (Cold) in morbidly obese subjects.

<p>Energy expenditure, body core temperature, mean skin temperature and core-skin temperature gradient in thermoneutral conditions (TN) and during mild cold (Cold) in morbidly obese subjects.</p