Agradecimentos: Guilherme Nogueira received financial support from the São Paulo Research Foundation (FAPESP #2014/24362-1). The authors thank Erika Roman, Joseane Morari, Marcio Cruz and Gerson Ferraz for laboratory management. The study was supported by grants from the São Paulo Research Foundation (2013/07607-8) and Conselho Nacional de Pesquisa e Desenvolvimento Cientifico. Funding São Paulo Research Foundation (FAPESP – 2013/07607-8). Consent for publication under Declaration Not applicable. Data availability Please contact author for data requests. São Paulo Research Foundation (FAPESP – 2013/07607-8) Ver menos

Abstract: 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 Ver menos