Zhu Kezhou, Liu Shanshan, Huang Yunying, Zhang Biyang, Houssein Nadia, Wu Jun
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Endocrinology. 2024 Nov 26;166(1). doi: 10.1210/endocr/bqae153.
Significant research interest has been focused on beige adipocytes, the activation of which improves glucose and lipid homeostasis, therefore representing new therapeutic opportunities for metabolic diseases. Various Cre/Lox-based strategies have been used to investigate the developmental history of beige adipocytes and how these cells adapt to environmental changes. Despite the significant advancement of our understanding of beige adipocyte biology, much of the molecular insights of the beige adipocyte, including its origin and cell type-specific function, remain to be further illustrated. It has previously been shown that Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) has selective functionality in beige adipocytes. In this study, we explore the Chrna2-Cre-driven reporter expression in mouse beige adipocytes in vivo and in vitro. Our findings indicate that Chrna2-Cre expression is present selectively in multiple locular beige adipocytes in subcutaneous inguinal white adipose tissue (iWAT) and differentiated stromal vascular fraction from iWAT. Chrna2-Cre expression was detected in iWAT of young pups and mice after cold exposure where a significant number of beige adipocytes are present. Chrna2-Cre-driven reporter expression is permanent in iWAT postlabeling and can be detected in the iWAT of adult mice or mice that have been housed extensively at thermoneutrality after cold exposure, even though only "inactive dormant" beige adipocytes are present in these mice. Chrna2-Cre expression can also be increased by rosiglitazone treatment and β-adrenergic activation. This research, therefore, introduces the Chrna2-Cre line as a valuable tool for tracking the development of beige adipocytes and investigating beige fat function.
大量研究兴趣集中在米色脂肪细胞上,其激活可改善葡萄糖和脂质稳态,因此为代谢性疾病带来了新的治疗机会。各种基于Cre/Lox的策略已被用于研究米色脂肪细胞的发育历程以及这些细胞如何适应环境变化。尽管我们对米色脂肪细胞生物学的理解有了显著进展,但米色脂肪细胞的许多分子见解,包括其起源和细胞类型特异性功能,仍有待进一步阐明。先前已表明,Chrna2(胆碱能受体烟碱型α2亚基)在米色脂肪细胞中具有选择性功能。在本研究中,我们在体内和体外探索了Chrna2-Cre驱动的报告基因在小鼠米色脂肪细胞中的表达。我们的研究结果表明,Chrna2-Cre表达选择性地存在于皮下腹股沟白色脂肪组织(iWAT)中的多个小室米色脂肪细胞以及来自iWAT的分化基质血管部分中。在幼崽和冷暴露后的小鼠的iWAT中检测到Chrna2-Cre表达,其中存在大量米色脂肪细胞。Chrna2-Cre驱动的报告基因表达在标记后的iWAT中持续存在,并且可以在成年小鼠或冷暴露后在热中性环境中广泛饲养的小鼠的iWAT中检测到,即使这些小鼠中仅存在“无活性休眠”的米色脂肪细胞。罗格列酮治疗和β-肾上腺素能激活也可增加Chrna2-Cre表达。因此,本研究将Chrna2-Cre品系作为追踪米色脂肪细胞发育和研究米色脂肪功能的有价值工具进行了介绍。