Abstract
SummaryCurrent understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent 18fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by 133xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate.
Highlights
The identification of brown adipose tissue (BAT) in adult humans offers the possibility of activating this tissue to treat metabolic disease
Study Visit 2: Measurement of BAT Activity Using Microdialysis Microdialysis catheters were placed in supraclavicular BAT and abdominal subcutaneous white adipose tissue (WAT) (Figure S1). 133Xenon was injected into BAT and WAT to measure blood flow continuously (Astrup et al, 1985)
Glucose concentrations in BAT were lower compared with WAT (Figure 2A), indicating substantial glucose uptake by BAT in warm conditions not typically associated with thermogenesis
Summary
The identification of brown adipose tissue (BAT) in adult humans offers the possibility of activating this tissue to treat metabolic disease. PET/CT (most commonly using 18fluorodeoxyglucose [18FDG]) has been relied upon to infer that BAT is activated by cold (Saito et al, 2009; Virtanen et al, 2009), is under sympathetic regulation (Cypess et al, 2015), contributes to non-shivering thermogenesis (Ouellet et al, 2012), enhances insulin sensitivity (Lee et al, 2014), and regulates lipid metabolism (Chondronikola et al, 2016) While these findings show that human and rodent BAT share substantial similarities, there are important differences in the regulation of BAT activation (Ramage et al, 2016), highlighting the need to dissect BAT physiology in humans. Alternative in vivo techniques used to study human BAT, such as measurement of supraclavicular temperature (Lee et al, 2011; Ramage et al, 2016), MRI
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