Interleukin-17 (IL-17) is expressed in the intestine in response to changes in the gut microbiome landscape and plays an important role in intestinal and systemic inflammatory diseases. There is evidence that dietary factors can also modify the expression of intestinal IL-17. Here, we hypothesized that, similar to several other gut-produced factors, IL-17 may act in the hypothalamus to modulate food intake. We confirm that food intake increases IL-17 expression in the mouse ileum and human blood. There is no expression of IL-17 in the hypothalamus; however, IL-17 receptor A is expressed in both pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons. Upon systemic injection, IL-17 promoted a rapid increase in hypothalamic POMC expression, which was followed by a late increase in the expression of AgRP. Both systemic and intracerebroventricular injections of IL-17 reduced calorie intake without affecting whole-body energy expenditure. Systemic but not intracerebroventricular injection of IL-17 increase brown adipose tissue temperature. Thus, IL-17 is a gut-produced factor that is controlled by diet and modulates food intake by acting in the hypothalamus. Our findings provide the first evidence of a cytokine that is acutely regulated by food intake and plays a role in the regulation of eating.

中文翻译：

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白细胞介素 17 作用于下丘脑，减少食物摄入

白细胞介素 17 (IL-17) 在肠道中表达以响应肠道微生物组景观的变化，并在肠道和全身炎症性疾病中发挥重要作用。有证据表明饮食因素也可以改变肠道 IL-17 的表达。在这里，我们假设，与其他几种肠道产生的因子相似，IL-17 可能在下丘脑中起作用以调节食物摄入。我们证实食物摄入会增加小鼠回肠和人体血液中 IL-17 的表达。下丘脑中无 IL-17 表达；然而，IL-17 受体 A 在阿片黑皮质素原 (POMC) 和刺鼠相关肽 (AgRP) 神经元中均有表达。全身注射后，IL-17 促进下丘脑 POMC 表达的快速增加，随后是 AgRP 表达的晚期增加。IL-17 的全身和脑室内注射都减少了卡路里摄入，而不影响全身能量消耗。全身而非脑室内注射 IL-17 会增加棕色脂肪组织的温度。因此，IL-17 是一种肠道产生的因子，受饮食控制并通过作用于下丘脑来调节食物摄入。我们的研究结果提供了第一个证据表明细胞因子受到食物摄入的剧烈调节并在饮食调节中发挥作用。