Early-life high-fat diet accelerates the development of vagal satiation signaling and predisposes females to overconsumption.

Overconsumption of foods rich in fats, sugars, and calories is a major contributing factor to increased risk for cardiometabolic disease. Ingestive experience with these foods can begin early in children, yet there is limited understanding of the impact of early life nutrition on the development of vagal afferent neurons necessary for coordinating appetitive and satiating behaviors. To address this gap, mice reared on a chow diet (control) were compared to those reared on a high-fat diet (HFDEARLY). We demonstrate that the vagally mediated satiation response to cholecystokinin (CCK) does not mature until adolescence in chow-reared mice. However, HFDEARLY exposure triggers a precocious maturation of this response, accompanied by transcriptomic changes in the nodose ganglion. Durable changes in orosensory processing and appetitive behaviors are also evident in adult female HFDEARLY mice, which consume more lipid and calorie-dense liquid diet than controls, suggesting a lasting, sex-specific vulnerability to overconsumption of palatable, energy-dense foods.