脂肪细胞是代谢和能量平衡的关键调节因子。白色脂肪细胞功能异常是肥胖相关疾病的特征，而产热脂肪细胞与心血管代谢健康相关。脂肪细胞通过在白色和产热表型之间的功能转换来动态适应环境信号，对这种可塑性的分子理解可能有助于改善代谢。在本文中，我们表明长链非编码RNA凋亡相关转录本在膀胱癌（AATBC）是人类特有的脂肪细胞可塑性调控因子。通过比较人类脂肪组织和培养脂肪细胞的转录谱，我们发现在产热条件下AATBC富集。我们利用原代和永生化的人类脂肪细胞发现AATBC增强了产热表型，这与呼吸增加和线粒体网络更加碎片化相关。在小鼠脂肪组织中表达AATBC导致血浆瘦素水平降低。有趣的是，这种关联在人类受试者中也存在，因为脂肪组织中的AATBC与血浆瘦素水平、BMI和其他代谢健康指标呈负相关。总之，AATBC是人类脂肪细胞可塑性和线粒体功能的新型与肥胖相关的调节因子。© 2023 The Authors. 根据CC BY NC ND 4.0许可发布。

Adipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, thermogenic adipocytes are linked to cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this plasticity could help improving metabolism. Here, we show that the lncRNA Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Comparing transcriptional profiles of human adipose tissues and cultured adipocytes we discovered that AATBC was enriched in thermogenic conditions. Using primary and immortalized human adipocytes we found that AATBC enhanced the thermogenic phenotype, which was linked to increased respiration and a more fragmented mitochondrial network. Expression of AATBC in adipose tissue of mice led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, BMI, and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.