Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
Diabetes. 2012 Dec;61(12):3106-13. doi: 10.2337/db12-0288. Epub 2012 Aug 7.
Brown adipose tissue (BAT) is currently considered as a target to combat obesity and diabetes in humans. BAT is densely innervated by the sympathetic nervous system (SNS) and can be stimulated by β-adrenergic agonists, at least in animals. However, the exact role of the β-adrenergic part of the SNS in BAT activation in humans is not known yet. In this study, we measured BAT activity by 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) positron emission tomography/computed tomography imaging in 10 lean men during systemic infusion of the nonselective β-agonist isoprenaline (ISO) and compared this with cold-activated BAT activity. ISO successfully mimicked sympathetic stimulation as shown by increased cardiovascular and metabolic activity. Energy expenditure increased to similar levels as during cold exposure. Surprisingly, BAT was not activated during β-adrenergic stimulation. We next examined whether the high plasma free fatty acid (FFA) levels induced by ISO competed with glucose ([(18)F]FDG) uptake in BAT locations by blocking lipolysis with acipimox (ACI). ACI successfully lowered plasma FFA, but did not increase [(18)F]FDG-uptake in BAT. We therefore conclude that systemic nonselective β-adrenergic stimulation by ISO at concentrations that increase energy expenditure to the same extent as cold exposure does not activate BAT in humans, indicating that other tissues are responsible for the increased β-adrenergic thermogenesis.
棕色脂肪组织 (BAT) 目前被认为是人类对抗肥胖和糖尿病的靶点。BAT 被交感神经系统 (SNS) 密集支配，可以被β-肾上腺素能激动剂刺激，至少在动物中是这样。然而，SNS 的β-肾上腺素能部分在人类 BAT 激活中的确切作用尚不清楚。在这项研究中，我们在 10 名瘦人中通过 2-脱氧-2-[(18)F]氟代-D-葡萄糖 ([(18)F]FDG) 正电子发射断层扫描/计算机断层扫描成像测量 BAT 活性，同时比较了冷激活的 BAT 活性。ISO 成功模拟了交感神经刺激，表现为心血管和代谢活动增加。能量消耗增加到与暴露在寒冷中相似的水平。令人惊讶的是，在β-肾上腺素能刺激期间 BAT 没有被激活。接下来，我们检查了 ISO 诱导的高血浆游离脂肪酸 (FFA) 水平是否通过用 acipimox (ACI) 阻断脂肪分解来竞争 BAT 部位的葡萄糖 ([(18)F]FDG) 摄取。ACI 成功降低了血浆 FFA，但并未增加 BAT 中的 [(18)F]FDG 摄取。因此，我们得出结论，ISO 以与寒冷暴露相同的程度增加能量消耗的全身非选择性β-肾上腺素能刺激不会激活人类的 BAT，表明其他组织负责增加的β-肾上腺素能产热。
