Differences in [18F]FDG uptake in BAT of UCP1 −/− and UCP1 +/+ during adrenergic stimulation of non-shivering thermogenesis

Abstract

Background 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. 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.

Xenon‐enhanced computed tomography assessment of brown adipose tissue distribution and perfusion in lean, obese, and diabetic primates

“…As a result, a wide range of conclusions about BAT distribution is inevitable when quantifying this tissue with 18 F-FDG standardized uptake values [11,12]. Additionally, although 18 F-FDG-PET has suggested that BAT activity is significantly lower in patients with obesity compared with lean patients [13], the dissociation between BAT activity and glucose uptake has demonstrated that these results may not be reliable [9,10,14]. Computed tomography (CT) and magnetic resonance imaging have also been explored as a method of locating and quantifying BAT [15,16], but their results depend on BAT hydration [17].…”

“…The use of NHPs in this study is motivated by their phylogenetic similarity with humans in terms of adipose distributions and progression of obesity and metabolic diseases [29]. In contrast to mice, which tend to have BAT predominantly concentrated in the interscapular region [14,19,26], humans and NHPs have very similar anatomical distributions of BAT, with the main depots located in the supraclavicular and axillary regions [30,31]. Rhesus and vervet monkeys, in particular, spontaneously develop obesity and diabetes as they age at prevalence rates comparable to that of humans [31].…”

In-vivo detection of white adipose tissue browning: a multimodality imaging approach

“…Additionally, the reduced volume of inguinal fat and the observed heterogeneity of the browning process in this tissue, coupled with the limited resolution of PET will make any quantification extremely challenging. MR thermometry and infrared thermometry have been used by us 34,40,41 and others 42,43 to assess thermogenic activity of the main BAT depot in vivo. However, decoupling the increase in thermogenic activity of the inguinal depot from the much larger increase www.nature.com/scientificreports/ in thermogenic activity of BAT will be impossible, especially considering that in anesthetized mice thermogenic activity in BAT alone can increase whole body temperature by several degrees Celsius 40 .…”

Longitudinal imaging of murine atherosclerosis with 2-deoxy-2-[18F]fluoro-D-glucose and [18F]-sodium fluoride in genetically modified Apolipoprotein E knock-out and wild type mice

“…Mice are known to have brown adipose tissue (BAT) in the neck region which is prone to accumulate [ 18 F]FDG. Proximity of brown fat as well as myocardial tissue to arterial segments poses a challenge in vascular imaging 26 , 27 . Accumulation in brown fat was minimized by assuring that the mice were kept warm at all times following tracer injection and during scans.…”