Fat body glycolysis defects inhibit mTOR and promote distant muscle disorganization through TNF-α/egr and ImpL2 signaling in Drosophila larvae.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-10-01 Epub Date: 2024-09-09 DOI:10.1038/s44319-024-00241-3

Miriam Rodríguez-Vázquez, Jennifer Falconi, Lisa Heron-Milhavet, Patrice Lassus, Charles Géminard, Alexandre Djiane

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Abstract

The fat body in Drosophila larvae functions as a reserve tissue and participates in the regulation of organismal growth and homeostasis through its endocrine activity. To better understand its role in growth coordination, we induced fat body atrophy by knocking down several key enzymes of the glycolytic pathway in adipose cells. Our results show that impairing the last steps of glycolysis leads to a drastic drop in adipose cell size and lipid droplet content, and downregulation of the mTOR pathway and REPTOR transcriptional activity. Strikingly, fat body atrophy results in the distant disorganization of body wall muscles and the release of muscle-specific proteins in the hemolymph. Furthermore, we showed that REPTOR activity is required for fat body atrophy downstream of glycolysis inhibition, and that the effect of fat body atrophy on muscles depends on the production of TNF-α/egr and of the insulin pathway inhibitor ImpL2.

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在果蝇幼虫体内，脂肪体糖酵解缺陷通过 TNF-α/egr 和 ImpL2 信号传导抑制 mTOR 并促进远端肌肉紊乱。

果蝇幼虫的脂肪体具有储备组织的功能，并通过其内分泌活动参与调节机体的生长和平衡。为了更好地了解脂肪体在生长协调中的作用，我们通过敲除脂肪细胞中糖酵解途径的几个关键酶来诱导脂肪体萎缩。我们的研究结果表明，糖酵解最后步骤的损伤会导致脂肪细胞体积和脂滴含量急剧下降，并下调 mTOR 通路和 REPTOR 的转录活性。令人震惊的是，脂肪体萎缩导致体壁肌肉远端紊乱，并在血淋巴中释放出肌肉特异性蛋白。此外，我们还发现糖酵解抑制下游的脂肪体萎缩需要REPTOR活性，脂肪体萎缩对肌肉的影响取决于TNF-α/egr和胰岛素通路抑制剂ImpL2的产生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

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