Fatty acid mobilization from adipose tissue is mediated by CD36 posttranslational modifications and intracellular trafficking.

Fatty acid mobilization from adipose tissue is mediated by CD36 posttranslational modifications and intracellular trafficking.
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DOI:
10.1172/jci.insight.147057
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发表时间:
2021-09-08
期刊:
影响因子:
8
通讯作者:
Kolonin MG
Kolonin MG
中科院分区:
医学1区
文献类型:
--
作者:
Daquinag AC;Gao Z;Fussell C;Immaraj L;Pasqualini R;Arap W;Akimzhanov AM;Febbraio M;Kolonin MG

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控制脂肪组织中长链脂肪酸(LCFA)动员的机制还不清楚。在这里,我们研究了LCFA转运蛋白CD 36如何调节这一过程。通过使用组织特异性KO小鼠模型,我们表明脂肪细胞和内皮细胞中的CD 36介导LCFA沉积到脂肪组织中和从脂肪组织释放。我们证明了脂肪细胞和内皮细胞CD 36在促进肿瘤生长和脂肪组织来源的LCFA所赋予的化疗耐药性中的作用。我们发现,在脂肪细胞、内皮细胞和癌细胞中,CD 36的动态半胱氨酸S-酰化介导了细胞间LCFA转运。我们证明了脂肪细胞中的脂解诱导触发了CD 36脱酰和去糖基化,以及其与相互作用的蛋白质,抑制素-1(PHB)和膜联蛋白2(ANX 2)的解离。我们的数据表明,脂解触发小窝内吞和易位的CD 36从细胞膜的脂滴。这项研究表明,由外而内和由内而外的细胞LCFA运输的CD 36 S-酰化及其与PHB和ANX 2的相互作用的调节机制。
The mechanism controlling long-chain fatty acid (LCFA) mobilization from adipose tissue is not well understood. Here, we investigated how the LCFA transporter CD36 regulates this process. By using tissue-specific KO mouse models, we showed that CD36 in adipocytes and endothelial cells mediated both LCFA deposition into and release from adipose tissue. We demonstrated the role of adipocytic and endothelial CD36 in promoting tumor growth and chemoresistance conferred by adipose tissue–derived LCFAs. We showed that dynamic cysteine S-acylation of CD36 in adipocytes, endothelial cells, and cancer cells mediated intercellular LCFA transport. We demonstrated that lipolysis induction in adipocytes triggered CD36 deacylation and deglycosylation, as well as its dissociation from interacting proteins, prohibitin-1 (PHB) and annexin 2 (ANX2). Our data indicate that lipolysis triggers caveolar endocytosis and translocation of CD36 from the cell membrane to lipid droplets. This study suggests a mechanism for both outside-in and inside-out cellular LCFA transport regulated by CD36 S-acylation and its interactions with PHB and ANX2.
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