Ciliary sensing in tanycytes couples nutrient availability to metabolic regulation

Abstract

Body homeostasis relies on accurate communication between the brain and the periphery. Disruption of this communication can contribute to disease. Tanycytes are located at the interface of the cerebrospinal fluid (CSF), bloodstream, and hypothalamus, where they sense circulating nutrients and regulate neuroendocrine axes and metabolism. However, the mechanisms by which they sense CSF signals remain largely unclear. Recent evidence that tanycytes possess primary cilia -- key sensory organelles -- led us to hypothesize that tanycytic cilia function as sensory antennae that detect metabolic cues in the CSF. Here, we demonstrate that tanycytic cilia exhibit distinct morphologies across subtypes and physiological states. They respond dynamically to hormonal and nutrient availability; notably, excess oleic acid shortens cilia, promotes lipid droplet accumulation, and reduces Ca{superscript 2} responses to ATP and glucose. Disrupting cilia via knockdown of intraflagellar transport (IFT) genes produced similar defects and impaired autophagy. Finally, selective Ift88 knockout in tanycytes increased body weight and reduced thermogenic activity in female mice. These findings identify tanycytic cilia as key sensors regulating energy balance.