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bioRxiv · 10.64898/2026.02.23.707454

IL-1β engages distinct peripheral sensory circuits to suppress feeding across time

Hayes, N. W.·Xia, J. L.·Frydman, J. A.·Duran, M. J.·Gebis, K. K.·Lorch, C. M.·Province, H. S.·Tang, E.·Beutler, L. R.
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Abstract

Loss of appetite is a hallmark of acute and chronic inflammation, and sustained anorexia causes malnutrition and worsens disease outcomes. Interleukin-1{beta} (IL-1{beta}) is one of the most potently anorexigenic inflammatory cytokines, yet how it engages neural circuits that suppress feeding remains incompletely understood. Specifically, the role of peripheral sensory neurons in mediating IL-1{beta}-induced anorexia is unresolved. Here, using DREADD-mediated inhibition of discrete peripheral sensory neuron populations and fiber photometry, we show that IL-1{beta}-induced anorexia occurs in at least two temporally and mechanistically distinct phases. Shortly after IL-1{beta} administration, prostaglandin signaling through non-vagal sensory afferents rapidly inhibits hypothalamic AgRP neurons to suppress food intake. At later time points, anorexia becomes partially prostaglandin-independent and vagal afferent neuron-dependent. Our findings demonstrate that multiple molecular signals mediate IL-1{beta}-induced anorexia, and that diverse peripheral sensory pathways, including a previously unappreciated contribution from non-vagal afferents, are critical links between systemic inflammation and neural control of appetite.

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Hayes, N. W., Xia, J. L., Frydman, J. A., Duran, M. J., Gebis, K. K., Lorch, C. M., Province, H. S., Tang, E., Beutler, L. R.. 2026-02-24. IL-1β engages distinct peripheral sensory circuits to suppress feeding across time. https://doi.org/10.64898/2026.02.23.707454

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