Knockdown expression of Syndecan in the fat body impacts nutrient metabolism and the organismal response to environmental stresses in Drosophila melanogaster.
Knockdown expression of Syndecan in the fat body impacts nutrient metabolism and the organismal response to environmental stresses in Drosophila melanogaster.
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DOI：
10.1016/j.bbrc.2016.06.027
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发表时间：
2016-08-12
影响因子：
3.1
通讯作者：
De Luca M
中科院分区：
文献类型：
--
作者：
Eveland M;Brokamp GA;Lue CH;Harbison ST;Leips J;De Luca M
硫酸乙酰肝素蛋白聚糖是一种跨膜蛋白，参与多种生理过程，包括细胞-基质粘附和炎症。来自模型系统和人类的最新证据表明，syndecans在能量平衡和营养代谢调节中发挥作用。然而，仍有许多有待了解的机制，通过syndecans影响这些表型。此前，我们报道了D。与对照相比，黑腹菌Syndecan（Sdc）突变体的代谢活性降低。在这里，我们敲低了脂肪体（哺乳动物脂肪组织和肝脏的功能等同物）中的内源性Sdc表达，以研究对代谢的影响是否源于该组织。我们发现，在脂肪体中敲低Sdc会导致果蝇具有更高水平的糖原和脂肪，并且在饥饿期间存活更长时间，这可能是由于它们额外的能量储备和再生能力的增加。然而，与对照果蝇相比，它们对环境压力（例如细菌感染和寒冷）也更敏感，并且在正常进食条件下代谢活性降低。在相同的条件下，脂肪体Sdc减少增强参与甘油生成和甘油生成的基因的表达，并诱导AKT和细胞外信号调节激酶1/2（ERK 1/2）的磷酸化水平急剧下降。总之，这些发现强烈表明，果蝇脂肪体Sdc参与了一种机制，根据营养状况将资源转移到不同的生理功能。
The heparan sulfate proteoglycan syndecans are transmembrane proteins involved in multiple physiological processes, including cell-matrix adhesion and inflammation. Recent evidence from model systems and humans suggest that syndecans have a role in energy balance and nutrient metabolism regulation. However, much remains to be learned about the mechanisms through which syndecans influence these phenotypes. Previously, we reported that D. melanogaster Syndecan (Sdc) mutants had reduced metabolic activity compared to controls. Here, we knocked down endogenous Sdc expression in the fat body (the functional equivalent of mammalian adipose tissue and liver) to investigate whether the effects on metabolism originate from this tissue. We found that knocking down Sdc in the fat body leads to flies with higher levels of glycogen and fat and that survive longer during starvation, likely due to their extra energy reserves and an increase in gluconeogenesis. However, compared to control flies, they are also more sensitive to environmental stresses (e.g. bacterial infection and cold) and have reduced metabolic activity under normal feeding conditions. Under the same conditions, fat-body Sdc reduction enhances expression of genes involved in glyceroneogenesis and gluconeogenesis and induces a drastic decrease in phosphorylation levels of AKT and extracellular signal regulated kinase 1/2 (ERK1/2). Altogether, these findings strongly suggest that Drosophila fat body Sdc is involved in a mechanism that shifts resources to different physiological functions according to nutritional status.