Berry Daniel C, Jiang Yuwei, Graff Jonathan M
Division of Endocrinology, Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9148, USA.
Department of Developmental Biology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, NB5.118, Dallas, Texas 75390-9148, USA.
Nat Commun. 2016 Jan 5;7:10184. doi: 10.1038/ncomms10184.
Cold temperatures induce formation of beige adipocytes, which convert glucose and fatty acids to heat, and may increase energy expenditure, reduce adiposity and lower blood glucose. This therapeutic potential is unrealized, hindered by a dearth of genetic tools to fate map, track and manipulate beige progenitors and 'beiging'. Here we examined 12 Cre/inducible Cre mouse strains that mark adipocyte, muscle and mural lineages, three proposed beige origins. Among these mouse strains, only those that marked perivascular mural cells tracked the cold-induced beige lineage. Two SMA-based strains, SMA-Cre(ERT2) and SMA-rtTA, fate mapped into the majority of cold-induced beige adipocytes and SMA-marked progenitors appeared essential for beiging. Disruption of the potential of the SMA-tracked progenitors to form beige adipocytes was accompanied by an inability to maintain body temperature and by hyperglycaemia. Thus, SMA-engineered mice may be useful to track and manipulate beige progenitors, beige adipocyte formation and function.
低温诱导米色脂肪细胞的形成，米色脂肪细胞可将葡萄糖和脂肪酸转化为热量，并可能增加能量消耗、减少肥胖和降低血糖。这种治疗潜力尚未实现，原因是缺乏用于对米色祖细胞和“米色化”进行谱系追踪、跟踪和操纵的基因工具。在这里，我们研究了12种标记脂肪细胞、肌肉和壁细胞谱系的Cre/诱导型Cre小鼠品系，这是三种推测的米色脂肪细胞起源。在这些小鼠品系中，只有那些标记血管周围壁细胞的品系能够追踪冷诱导的米色脂肪细胞谱系。两种基于平滑肌肌动蛋白（SMA）的品系，即SMA-Cre(ERT2)和SMA-rtTA，对大多数冷诱导的米色脂肪细胞进行了谱系追踪，并且SMA标记的祖细胞似乎对米色化至关重要。SMA追踪的祖细胞形成米色脂肪细胞的潜力受到破坏时，会伴随着无法维持体温和高血糖症。因此，利用SMA构建的小鼠可能有助于追踪和操纵米色祖细胞、米色脂肪细胞的形成和功能。
