Tanycytic ciliary calcium links metabolic sensing to appetite control

The central nervous system maintains energy balance by sensing the body’s metabolic state1,2, yet the precise cellular and molecular sensors involved remain elusive. Tanycytes, specialized glial cells lining the hypothalamic third ventricle, are strategically positioned to monitor systemic signals3-7, and their primary cilia — antenna-like organelles — are implicated in this process8 . However, whether and how these cilia translate metabolic information into a behavioral response is unknown. Here we show that tanycyte primary cilia are dynamic metabolic sensors whose length is remodeled by physiological and pathological states, such as fasting and obesity. Genetic ablation of these cilia in tanycytes exacerbates diet-induced obesity by impairing homeostatic control. Mechanistically, we uncover a two-stage, ciliary-to-cytoplasmic calcium relay: Sonic Hedgehog (SHH) signaling triggers a localized Ca²⁺ influx through the ciliary channel TRPC3, which serves as a spark to ignite a global calcium wave amplified by release from the endoplasmic reticulum. This signal governs tanycyte activity, which in turn gates a key hypothalamic anorexigenic circuit to suppress feeding. These findings identify a fundamental sensory mechanism that couples glial cells to neural circuits, establishing the tanycytic cilium as a critical regulator of appetite and a potential therapeutic target for obesity.