Beige adipocytes can be induced from white adipocytes and precursors upon stimulation by cold temperatures and act like brown adipocytes to increase energy expenditure. Most in vivo studies examining the mechanisms for the induction of beige adipocytes have focused on subcutaneous white adipose tissue (sWAT; benign fat) in the mouse. How intra-abdominal WAT (aWAT; malignant fat) develops into beige adipocytes remains obscure, largely because there is a lack of a good animal model for the induction of beige adipocytes from aWAT. To better understand the development of beige adipocytes from mammalian WATs, especially aWAT, we induced beige adipocytes from bat aWAT and mouse sWAT by exposure to cold temperatures and analyzed their molecular signatures. RNA sequencing followed by whole genome-wide expression analysis shows that beige adipocytes induced from bat aWAT, rather than sWAT, have molecular signatures resembling those of mouse sWAT-induced beige adipocytes and exhibit dynamic profiles similar to those of classical brown adipocytes. In addition, we identified molecular markers that were highly enriched in beige adipocytes and conserved between bat aWAT and mouse sWAT, a set that included the genes Uqcrc1 and Letm1. Furthermore, knockdown of Uqcrc1 and Letm1 expression shows that they are required not only for beige adipocyte differentiation but also for preadipocyte maturation. This study presents a new model for research into the induction of beige adipocytes from aWAT in vivo, which, when combined with models where beige adipocytes are induced from sWAT, provides insight into therapeutic approaches for combating obesity-related diseases in humans.

中文翻译：

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从体内腹腔内脂肪细胞诱导的米色脂肪细胞的分子标记和功能分析。

米色的脂肪细胞可以在低温刺激下由白色脂肪细胞和前体诱导而来，其作用类似于棕色脂肪细胞，以增加能量消耗。大多数研究米色脂肪细胞诱导机制的体内研究都集中在小鼠的皮下白色脂肪组织（sWAT；良性脂肪）上。腹腔内WAT（aWAT；恶性脂肪）如何发展成米色脂肪细胞仍然不清楚，这主要是因为缺乏从aWAT诱导米色脂肪细胞的良好动物模型。为了更好地了解哺乳动物WAT，尤其是aWAT中米色脂肪细胞的发育，我们通过暴露于低温下从蝙蝠aWAT和小鼠sWAT诱导了米色脂肪细胞，并分析了它们的分子特征。RNA测序和全基因组全表达分析表明，蝙蝠aWAT而不是sWAT诱导的米色脂肪细胞具有类似于小鼠sWAT诱导的米色脂肪细胞的分子特征，并且表现出与经典棕色脂肪细胞相似的动态特性。此外，我们鉴定了高度富含米色脂肪细胞且在蝙蝠aWAT和小鼠sWAT之间保守的分子标记物，其中包括基因Uqcrc1和Letm1。此外，敲低Uqcrc1和Letm1表达表明它们不仅是米色脂肪细胞分化所必需的，而且是脂肪前细胞成熟所必需的。这项研究提供了一种新的模型，用于研究体内从aWAT诱导米色脂肪细胞的方法，当与从sWAT诱导米色脂肪细胞的模型相结合时，将为对抗人类肥胖相关疾病的治疗方法提供见识。