Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling.
Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling.
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DOI：
10.1534/g3.117.300416
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发表时间：
2018-01-04
期刊：
影响因子：
--
通讯作者：
Savage-Dunn C
中科院分区：
文献类型：
--
作者：
Clark JF;Meade M;Ranepura G;Hall DH;Savage-Dunn C
代谢稳态是由多种输入协调控制的。了解这些调节网络对于对抗代谢紊乱至关重要。秀丽隐杆线虫已经成为一个强大的，遗传上可处理的模型系统，用于发现脂质调节机制。本文介绍了秀丽隐杆线虫骨形态发生蛋白2/4 （BMP2/4）同源物DBL-1作为脂质稳态的重要调节因子。我们使用中性脂质染色和脂滴标记物来证明DBL-1/BMP信号的增加和减少导致脂储存和脂滴计数的减少。然而，我们发现脂滴大小与DBL-1/BMP信号水平呈正相关。肠道内脂质积累的调节是通过非细胞自主信号传导发生的，因为Smad信号传感器SMA-3在表皮（皮下）的表达足以挽救脂质积累的损失。最后，遗传学证据表明，DBL-1/BMP在脂质代谢中作用于胰岛素/IGF-1信号的上游。我们得出结论，BMP信号通过向胰岛素通路的器官间信号调节秀丽隐杆线虫的脂质代谢，从而揭示了一个尚未被充分研究的代谢稳态调节机制。
Metabolic homeostasis is coordinately controlled by diverse inputs. Understanding these regulatory networks is vital to combating metabolic disorders. The nematode Caenorhabditis elegans has emerged as a powerful, genetically tractable model system for the discovery of lipid regulatory mechanisms. Here we introduce DBL-1, the C. elegans homolog of bone morphogenetic protein 2/4 (BMP2/4), as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level of DBL-1/BMP signaling. Regulation of lipid accumulation in the intestine occurs through non-cell-autonomous signaling, since expression of SMA-3, a Smad signal transducer, in the epidermis (hypodermis) is sufficient to rescue the loss of lipid accumulation. Finally, genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism in C. elegans through interorgan signaling to the Insulin pathway, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.
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影响因子：
7
作者：
Ritter, Ashlyn D.;Shen, Yuan;Walhout, Albertha J. M.
通讯作者：
Walhout, Albertha J. M.
DOI：
10.1016/j.bbrc.2006.04.030
发表时间：
2006-06-16
影响因子：
3.1
作者：
Sjoholm, Kajsa;Palming, Jenny;Carlsson, Lena M. S.
通讯作者：
Carlsson, Lena M. S.
影响因子：
64.5
作者：
Böhni, R;Riesgo-Escovar, J;Hafen, E
通讯作者：
Hafen, E
DOI：
10.1073/pnas.93.2.790
发表时间：
1996-01-23
影响因子：
11.1
作者：
Savage, C;Das, P;Padgett, RW
通讯作者：
Padgett, RW
影响因子：
64.5
作者：
BAKER, J;LIU, JP;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A