Ghrelin drives food intake by attentional bias towards food cues

The global rise in overweight and obesity underscores the need to understand mechanisms driving overconsumption. Food-predictive cues are potent environmental triggers and their impact on behaviour is modulated by attentional processes. Attentiveness to such cues increases during fasting, when circulating levels ghrelin, a hunger hormone, also increases. Ghrelin positively correlates with neural responses to visual food cues, yet its role in attentional engagement with conditioned food cues remains unclear. We developed a novel home-cage operant task using the Feeding Experimentation 3 (FED3) device to assess attention-linked behaviours towards a conditioned food cue in male C57BL/6J mice. Mice progressed through staged training and were tested with increasing attentional load across three conditions: fed, overnight fasted and subcutaneous ghrelin-injection using a cross-over design. Both fasting and ghrelin significantly increased correct and premature responses, while reducing omissions, indicating enhanced attentiveness. Importantly, ghrelin did not increase non-cued food intake; its effect on consumption occurred only when food was signalled by the conditioned cue. In contrast, fasting increased both non-cued and cued intake. Feeding rate was elevated under both conditions, but only in the presence of the cue. These findings validate a novel paradigm for assessing attention to food cues and demonstrate that fasting and ghrelin enhance attentional engagement that translates into cue-driven consumption. This highlights the importance of hunger signals in food cue reactivity and overconsumption, warranting further investigation into the neural mechanisms linking ghrelin action with attentional control.