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Kaushik et al.1 report that a similar pathway operates in AgRP neurons, with consequences that seem to extend beyond fuel utilization. They propose that AgRP neurons accumulate free fatty acids from the blood during food deprivation and that these fatty acids are then quickly converted into triglyceride fats and stored in lipid droplets (Fig. 1). These lipids are rapidly remobilized through autophagy of the lipid droplet, and free fatty acids are re-formed for use as fuel. The authors suggest that this circuitous pathway provides a mechanism for regulatory control over the accumulation of free fatty acids in the cell, so that they can be used in an orderly fashion. It remains to be seen whether this process operates in other neurons. 一种吞噬作用把脂肪酸吸收
A key finding from these experiments is that Agrp expression, which promotes eating, is increased by free fatty acids. In addition, this effect on gene expression requires lysosomal processing, as would be expected of the autophagy pathway.
扰乱小鼠的脂质摄取会导致明显后果。利用遗传敲除AGRP神经元细胞自噬途径的一个重要组分后,作者发现,相对于对照组,小鼠在剥夺食物后再进食也吃得更少了,体重也下降了。他们后续研究揭示,这些小鼠的AGRP神经肽表达下调了,他们认为这就是为什么小鼠吃得更少,重量更轻了。These results1 should be considered in the light of other studies demonstrating a role for fatty-acid metabolism in the regulation of Agrp expression. For example, Agrp expression is reduced when fatty-acid utilization is inhibited by eliminating an uncoupling protein involved in the activity of the mitochondrion, the cell's energy-producing organelle6. One implication is that the autophagy pathway could be linked to the transport of fatty acids for mitochondrial metabolism. Then there is the question of how cellular fatty acids regulate Agrp. One possibility for future investigation is the involvement of the transcription factor FoxO1, which regulates Agrp expression according to hunger status7.
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目前尚不清楚是否中断 在 AGRP神经细胞自噬途径 对调节摄食和体重只通过这里描述的脂质处理机制。所以必须探索这一途径中AGRP神经元的电活动,对它们的发育,以及它们与其他AGRP神经功能的调节子,如突触的输入和激素调节的互动, which I been working on:)Could blocking this cannibalistic process be used to reduce body weight? Possibly, but the autophagy pathway is ubiquitous in cells throughout the body, so extensive investigation will be needed to find selective points of entry for therapeutic interference in obesity and eating disorders.
”这篇报道的核心就是FFA脂肪酸影响AgRP神经元活性,从而触发饥饿并诱导摄食“原文:
Metabolism: Let them eat fat附件: 477166a.pdf
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