The hypothalamus plays a central role in monitoring and regulating systemic glucose metabolism. The brain is enriched with phospholipids containing poly-unsaturated fatty acids, which are biologically active in physiological regulation. Here, we show that intraperitoneal glucose injection induced changes in hypothalamic distribution and amount of phospholipids, especially arachidonic-acid-containing phospholipids, that were then metabolized to produce prostaglandins. Knockdown of cytosolic phospholipase A2 (cPLA2), a key enzyme for generating arachidonic acid from phospholipids, in the hypothalamic ventromedial nucleus (VMH), lowered insulin sensitivity in muscles during regular chow diet (RCD) feeding. Conversely, the down-regulation of glucose metabolism by high fat diet (HFD) feeding was improved by knockdown of cPLA2 in the VMH through changing hepatic insulin sensitivity and hypothalamic inflammation. Our data suggest that cPLA2-mediated hypothalamic phospholipid metabolism is critical for controlling systemic glucose metabolism during RCD, while continuous activation of the same pathway to produce prostaglandins during HFD deteriorates glucose metabolism.

中文翻译：

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腹侧下丘脑中的前列腺素调节外周葡萄糖代谢

下丘脑在监测和调节全身性葡萄糖代谢中起着核心作用。大脑富含富含多不饱和脂肪酸的磷脂，这些磷脂在生理调节中具有生物活性。在这里，我们显示腹膜内注射葡萄糖诱导下丘脑分布和磷脂量（尤其是含花生四烯酸的磷脂）发生变化，然后被代谢产生前列腺素。在下丘脑腹膜外核（VMH）中抑制胞质磷脂酶A2（cPLA2）是一种从磷脂产生花生四烯酸的关键酶，它在常规食物（RCD）喂养期间降低了肌肉的胰岛素敏感性。反过来，通过改变肝胰岛素敏感性和下丘脑炎症，通过降低VMH中的cPLA2可以改善高脂饮食（HFD）喂养对葡萄糖代谢的下调作用。我们的数据表明，cPLA2介导的下丘脑磷脂代谢对于控制RCD期间的全身葡萄糖代谢至关重要，而在HFD期间持续激活相同途径产生前列腺素会恶化葡萄糖代谢。