Abstract
BackgroundIn vivo imaging of glucose analogue 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) via positron emission tomography (PET) is the current gold standard to visualize and assess brown adipose tissue (BAT) activity. However, glucose metabolism is only a part of the metabolic activity of BAT. [18F]FDG-PET has been shown in clinical trials to often fail to visualize BAT under insulin-resistant conditions associated with aging and weight gain. We employed a novel developed triglyceride-based tracer to visualize BATs metabolic activity under different temperature conditions as well as under diabetic and obese conditions in preclinical models.Results[18F]BDP-TG-chylomicron-like particles visualized BAT in control, streptozocin-induced diabetes and obese mice. Increased BAT tracer uptake was found in control mice acutely exposed to cold but not in cold-acclimated animals. Diabetes did not remove BAT tracer uptake, but did limit BAT tracer uptake to levels of control mice housed at 21 °C. In obese animals, BAT tracer uptake was significantly reduced, although the stimulating effect of cold exposure could still be noted.ConclusionBAT was visualized in control, diabetic and obese conditions. Streptozocin-induced diabetes, but not obesity, inhibited the stimulatory effect of cold exposure.
Highlights
In vivo imaging of glucose analogue 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) via positron emission tomography (PET) is the current gold standard to visualize and assess brown adipose tissue (BAT) activity
Norepinephrine binding to β3-adrenoreceptors on brown adipocytes activates a signaling cascade, which will lead to lipolysis of intracellular triglycerides (TGs) and at the end result in uncoupling protein 1 (UCP1) activation [6, 7]
We investigate the effect of induced diabetes and obesity as well as acute cold and cold acclimation in a mouse model on BAT metabolism visualized by our recently developed lipid-based tracer [18F] BODIPY ([18F]BDP)-TG-chylomicron-like particle ([18F] BDP-TG)
Summary
In vivo imaging of glucose analogue 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) via positron emission tomography (PET) is the current gold standard to visualize and assess brown adipose tissue (BAT) activity. Results: [18F]BDP-TG-chylomicron-like particles visualized BAT in control, streptozocin-induced diabetes and obese mice. BAT tracer uptake was significantly reduced, the stimulating effect of cold exposure could still be noted. BAT has the ability to uncouple its ATP production and to produce heat instead of ATP During this process, protons enter the mitochondrial matrix by uncoupling protein 1 (UCP1) [1], a BAT and beige fat specific protein, and release their energy as heat [2, 3]. Protons enter the mitochondrial matrix by uncoupling protein 1 (UCP1) [1], a BAT and beige fat specific protein, and release their energy as heat [2, 3] This process is known as nonshivering thermogenesis [2, 4]. BAT might be an interesting target in the fight against obesity as it “burns” lipids instead of storing them
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