Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8200, Aarhus N, Denmark.
Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Int J Obes (Lond). 2020 Jun;44(6):1417-1427. doi: 10.1038/s41366-020-0533-7. Epub 2020 Jan 21.
BACKGROUND/OBJECTIVES: Brown adipose tissue (BAT) has gained growing interest as a potential target for treatment of obesity. Currently, the most widely used technique/method for in vivo measurements of BAT activity in humans is FDG PET/CT. To supplement these investigations novel radiation-free methods are warranted. Deuterium metabolic imaging (DMI) is a novel modality that combines magnetic resonance spectroscopic (MRS) imaging with deuterium-labelled glucose (H-glucose). This allows for spatio-temporal and metabolic imaging beyond glucose uptake. We aimed to evaluate if DMI could discriminate glucose metabolism in BAT of cold-acclimatised and thermoneutral rats.
SUBJECTS/METHODS: Male Sprague-Dawley rats were housed in a cold environment (9 °C, n = 10) or at thermoneutrality (30 °C, n = 11) for 1 week. For imaging rats were anaesthetized, received a H-glucose (1 M, 1.95 g/kg) bolus and DMI was acquired at baseline followed by 20 min time intervals up to 2 h. Furthermore, Dixon MRI was performed for anatomical determination of the interscapular BAT (iBAT) depot along with dynamic contrast enhanced (DCE) MRI to evaluate perfusion.
H-glucose signal was higher in cold-acclimatised rats compared with thermoneutral rats (p ≤ 0.001) indicating an overall increase in glucose uptake and metabolism. This was in line with a lower fat/water threshold, higher perfusion and increased UCP1 mRNA expression in iBAT (ninefold increment) of cold-acclimatised rats compared with thermoneutral rats.
We find that DMI can discriminate cold-acclimatised and thermoneutral BAT in rats. This is the first study to evaluate BAT activity by DMI, which may open up for the use of the non-radioactive DMI method for BAT measurements in humans.
背景/目的:棕色脂肪组织(BAT)作为肥胖治疗的潜在靶点,受到越来越多的关注。目前,用于人体 BAT 活性的体内测量最广泛的技术/方法是 FDG PET/CT。为了补充这些研究,需要新的无辐射方法。氘代谢成像(DMI)是一种新的方式,它将磁共振光谱(MRS)成像与氘标记的葡萄糖(H-葡萄糖)结合在一起。这使得时空和代谢成像超越了葡萄糖摄取。我们旨在评估 DMI 是否可以区分冷适应和热中性大鼠的 BAT 中的葡萄糖代谢。
受试者/方法:雄性 Sprague-Dawley 大鼠分别在冷环境(9°C,n=10)或热中性环境(30°C,n=11)中饲养 1 周。在成像时,大鼠被麻醉,接受 H-葡萄糖(1M,1.95g/kg)脉冲注射,在基线时进行 DMI 采集,然后在 20 分钟的时间间隔内采集至 2 小时。此外,还进行了 Dixon MRI 以解剖确定肩胛间 BAT(iBAT)库,以及动态对比增强(DCE)MRI 以评估灌注。
与热中性大鼠相比,冷适应大鼠的 H-葡萄糖信号更高(p≤0.001),表明葡萄糖摄取和代谢整体增加。这与冷适应大鼠的脂肪/水阈值较低、灌注较高和 iBAT 中 UCP1 mRNA 表达增加(增加九倍)相一致。
我们发现 DMI 可以区分冷适应和热中性的 BAT。这是首次使用 DMI 评估 BAT 活性的研究,这可能为非放射性 DMI 方法在人体 BAT 测量中的应用开辟了道路。