Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.
Ageing Res Rev. 2010 Jan;9(1):69-76. doi: 10.1016/j.arr.2009.11.004. Epub 2009 Dec 5.
The most commonly studied laboratory rodents possess a specialized form of fat called brown adipose tissue (BAT) that generates heat to help maintain body temperature in cold environments. In humans, BAT is abundant during embryonic and early postnatal development, but is absent or present in relatively small amounts in adults where it is located in paracervical and supraclavicular regions. BAT cells can 'burn' fatty acid energy substrates to generate heat because they possess large numbers of mitochondria in which oxidative phosphorylation is uncoupled from ATP production as a result of a transmembrane proton leak mediated by uncoupling protein 1 (UCP1). Studies of rodents in which BAT levels are either increased or decreased have revealed a role for BAT in protection against diet-induced obesity. Data suggest that individuals with low levels of BAT are prone to obesity, insulin resistance and cardiovascular disease, whereas those with higher levels of BAT maintain lower body weights and exhibit superior health as they age. BAT levels decrease during aging, and dietary energy restriction increases BAT activity and protects multiple organ systems including the nervous system against age-related dysfunction and degeneration. Future studies in which the effects of specific manipulations of BAT levels and thermogenic activity on disease processes in animal models (diabetes, cardiovascular disease, cancers, neurodegenerative diseases) are determined will establish if and how BAT affects the development and progression of age-related diseases. Data from animal studies suggest that BAT and mitochondrial uncoupling can be targeted for interventions to prevent and treat obesity and age-related diseases. Examples include: diet and lifestyle changes; specific regimens of mild intermittent stress; drugs that stimulate BAT formation and activity; induction of brown adipose cell progenitors in muscle and other tissues; and transplantation of brown adipose cells.
最常被研究的实验啮齿动物具有一种特殊形式的脂肪，称为棕色脂肪组织 (BAT)，它可以产生热量，帮助维持在寒冷环境中的体温。在人类中，BAT 在胚胎期和出生后早期发育过程中非常丰富，但在成年期却不存在或存在相对较少，主要位于颈部和锁骨区域。BAT 细胞可以“燃烧”脂肪酸能量底物来产生热量，因为它们拥有大量的线粒体，在线粒体中，氧化磷酸化与 ATP 产生解耦，这是由于解耦蛋白 1 (UCP1)介导的跨膜质子泄漏所致。对 BAT 水平增加或减少的啮齿动物的研究揭示了 BAT 在预防饮食诱导肥胖中的作用。数据表明，BAT 水平较低的个体容易肥胖、胰岛素抵抗和心血管疾病，而 BAT 水平较高的个体保持较低的体重，并随着年龄的增长表现出更好的健康状况。BAT 水平随着年龄的增长而下降，而饮食能量限制会增加 BAT 的活性，并保护包括神经系统在内的多个器官系统免受与年龄相关的功能障碍和退化。未来的研究将确定特定操纵 BAT 水平和产热活性对动物模型中疾病过程的影响（糖尿病、心血管疾病、癌症、神经退行性疾病），将确定 BAT 是否以及如何影响与年龄相关疾病的发展和进展。动物研究数据表明，BAT 和线粒体解耦可以作为干预措施的靶点，以预防和治疗肥胖和与年龄相关的疾病。这些干预措施包括：饮食和生活方式的改变；温和间歇性应激的特定方案；刺激 BAT 形成和活性的药物；在肌肉和其他组织中诱导棕色脂肪细胞前体；以及移植棕色脂肪细胞。
