Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function.

Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function.
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DOI:
10.1038/ncomms10184
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发表时间:
2016-01-05
影响因子:
16.6
通讯作者:
Graff JM
Graff JM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Berry DC;Jiang Y;Graff JM

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低温诱导米色脂肪细胞的形成,其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。这种治疗潜力是未实现的,阻碍了缺乏遗传工具的命运地图,跟踪和操纵米色祖细胞和“beiging”。在这里,我们研究了12 Cre/诱导Cre小鼠品系,标志着脂肪细胞,肌肉和壁谱系,三个建议米色的起源。在这些小鼠品系中,只有那些标记血管周围壁细胞的小鼠追踪到冷诱导的米色谱系。两种基于SMA的菌株SMA-CreERT 2和SMA-rtTA的命运映射到大多数冷诱导的米色脂肪细胞中,并且SMA标记的祖细胞对于米色化似乎是必需的。SMA追踪的祖细胞形成米色脂肪细胞的潜力的破坏伴随着无法维持体温和高脂血症。因此,SMA工程小鼠可用于跟踪和操纵米色祖细胞、米色脂肪细胞形成和功能。 米色脂肪细胞的形成是对寒冷的反应,被认为有助于生物体能量的稳态。在这里,作者研究了一系列条件性和诱导性RFP表达Cre小鼠品系,发现基于SMA的品系对于绘制米色脂肪细胞祖细胞最有用。
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-CreERT2 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. Beige adipocytes are formed in response to cold and thought to contribute to organismal energy homeostasis. Here, the authors study a range of conditional and inducible RFP-expressing Cre mouse strains and find that SMA-based lines are the most useful for mapping beige adipocyte progenitor cells.