Cutting Edge: Intestinal IL-17A Receptor Signaling Specifically Regulates High-Fat Diet-Mediated, Microbiota-Driven Metabolic Disorders

Previous studies indicate that IL-17A plays an important role in mediating the intestinal micro biota and systemic metabolic functions. However, it is not known where IL-17RA signaling occurs to mediate these effects. To investigate this question, we used intestinal epithelial -specific (Il17raIEC) and liver-specific (Il17raLiv e r) IL-17RA knockout mice as well as littermate control mice. Our results indicate that intestinal IL-17RA signaling helps mediate systemic metabolic functions upon exposure to prolonged high-fat diet. Il17raIEC mice display impaired glucose metabolism, altered hormone and adipokine levels, increased visceral adiposity, and greater hepatic lipid deposition when compared with their littermate controls. We show that IL-17RA-driven changes in microbiota composition are responsible for regulating systemic glucose metabolism. Altogether, our data elucidate the importance of intestinal IL-17RA signaling in regulating high-fat diet -mediated systemic glucose and lipid metabolism

Automated summary

The study investigates the role of intestinal IL-17RA signaling in mediating systemic metabolic functions under prolonged high-fat diet conditions. It shows that IL-17RA-driven changes in microbiota composition regulate systemic glucose metabolism, emphasizing the importance of intestinal IL-17RA signaling in high-fat diet-mediated systemic glucose and lipid metabolism.