A lipase-independent pathway of lipid release and immune modulation by adipocytes

A lipase-independent pathway of lipid release and immune modulation by adipocytes
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DOI:
10.1126/science.aaw2586
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发表时间:
2019-03-01
期刊:
影响因子:
56.9
通讯作者:
Ferrante, Anthony W., Jr.
Ferrante, Anthony W., Jr.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Flaherty, Stephen E., III;Grijalva, Ambar;Ferrante, Anthony W., Jr.

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为了满足全身代谢需要,脂肪细胞通过中性脂肪酶的作用释放脂肪酸和甘油。在这里,我们描述了脂肪细胞脂质释放的次级途径,该途径独立于典型的脂肪分解。我们发现脂肪细胞释放外泌体大小的、充满脂质的囊泡(AdExos),成为局部巨噬细胞的脂质来源。瘦小鼠的脂肪组织每天通过离体外泌体释放其脂质含量的约 1%,这一速度在肥胖动物中增加了一倍多。 AdExos 和相关因子足以诱导骨髓前体体外分化为脂肪组织巨噬细胞样细胞。因此,AdExos 既是局部脂质释放的替代途径,也是实质细胞调节组织巨噬细胞分化和功能的机制。
To meet systemic metabolic needs, adipocytes release fatty acids and glycerol through the action of neutral lipases. Here, we describe a secondary pathway of lipid release from adipocytes that is independent of canonical lipolysis. We found that adipocytes release exosome-sized, lipid-filled vesicles (AdExos) that become a source of lipid for local macrophages. Adipose tissue from lean mice released similar to 1% of its lipid content per day via exosomes ex vivo, a rate that more than doubles in obese animals. AdExos and associated factors were sufficient to induce in vitro differentiation of bone marrow precursors into adipose tissue macrophage-like cells. Thus, AdExos are both an alternative pathway of local lipid release and a mechanism by which parenchymal cells can modulate tissue macrophage differentiation and function.