Abstract
BackgroundBrown adipose tissue (BAT) is a fat tissue found in most mammals that helps regulate energy balance and core body temperature through a sympathetic process known as non-shivering thermogenesis. BAT activity is commonly detected and quantified in [18F]FDG positron emission tomography/computed tomography (PET/CT) scans, and radiotracer uptake in BAT during adrenergic stimulation is often used as a surrogate measure for identifying thermogenic activity in the tissue. BAT thermogenesis is believed to be contingent upon the expression of the protein UCP1, but conflicting results have been reported in the literature concerning [18F]FDG uptake within BAT of mice with and without UCP1. Differences in animal handling techniques such as feeding status, type of anesthetic, type of BAT stimulation, and estrogen levels were identified as possible confounding variables for [18F]FDG uptake. In this study, we aimed to assess differences in BAT [18F]FDG uptake between wild-type and UCP1-knockout mice using a protocol that minimizes possible variations in BAT stimulation caused by different stress responses to mouse handling.Results[18F]FDG PET/CT scans were run on mice that were anesthetized with pentobarbital after stimulation of non-shivering thermogenesis by norepinephrine. While in wild-type mice [18F]FDG uptake in BAT increased significantly with norepinephrine stimulation of BAT, there was no consistent change in [18F]FDG uptake in BAT of mice lacking UCP1.Conclusions[18F]FDG uptake within adrenergically stimulated BAT of wild-type and UCP1-knockout mice can significantly vary such that an [18F]FDG uptake threshold cannot be used to differentiate wild-type from UCP1-knockout mice. However, while an increase in BAT [18F]FDG uptake during adrenergic stimulation is consistently observed in wild-type mice, in UCP1-knockout mice [18F]FDG uptake in BAT seems to be independent of β3-adrenergic stimulation of non-shivering thermogenesis.
Highlights
Brown adipose tissue (BAT) is a fat tissue found in most mammals that helps regulate energy balance and core body temperature through a sympathetic process known as non-shivering thermogenesis
Several articles have extensively reported on the many limitations of [18F]FDG/PET for the detection of BAT activity [7, 8], even suggesting that adrenergically induced glucose uptake in brown adipose tissue is independent of BAT thermogenesis [11]
The aim of this study was to assess differences in BAT [18F]FDG uptake between WT and knockout mice lacking uncoupling protein 1 (UCP1) (KO) mice using a protocol that minimizes possible variations in BAT stimulation caused by a different stress response to mouse handling
Summary
Brown adipose tissue (BAT) is a fat tissue found in most mammals that helps regulate energy balance and core body temperature through a sympathetic process known as non-shivering thermogenesis. [18F]FDG positron emission tomography/computed tomography (PET/CT) is the imaging technique most commonly used to assess BAT activity in rodents and humans [4, 7, 8] Often, in these scans, an absolute threshold for the standardized uptake value (SUV), a measure of radiotracer accumulation, is used to identify and quantify thermogenically active BAT in the supraclavicular fat depots of humans [7,8,9]. Several articles have extensively reported on the many limitations of [18F]FDG/PET for the detection of BAT activity [7, 8], even suggesting that adrenergically induced glucose uptake in brown adipose tissue is independent of BAT thermogenesis [11] These results seem to indicate that the high variability seen in human BAT glucose uptake [12, 13] may not be due to true differences in BAT thermogenesis [14], but to differences in insulin sensitivity and tissue blood flow [15]
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