The critical role of gut-brain signalling in eating behaviour and obesity

The process of eating can be divided into three distinct phases of behaviour: food seeking, food consumption and non-prandial activities. The durations of, and transitions between, these behavioural phases are driven by underlying interoceptive phenomena of hunger, satiation and satiety. The gut-brain axis regulates all eating phases, with the vagus nerve a primary conduit for interoceptive feedback about gut-derived mechanical and chemical cues. This Review explores the mechanisms governing each phase, focusing on how gut-derived signals are peripherally and centrally integrated to shape hunger, satiation and satiety, food preferences, and food-related learning. Chronic exposure to high-fat, high-sugar diets disrupts these mechanisms, driving a maladaptive state characterized by hyperphagia, food choice biases and habitual overeating. We examine the mechanisms underlying this maladaptive state, including vagal fibre remodelling, altered gene expression and leptin resistance, which can impair gut-brain communication, diminishing the brain's capacity to appropriately control eating behaviour and maintain energy balance. Emerging therapies, including glucagon-like peptide 1 receptor agonists, are effective in promoting weight loss but typically do not reverse the underlying causes of gut-brain axis dysfunction. By examining the mechanisms of gut-brain signalling, this Review highlights the vagus nerve as a key, yet underappreciated, target for obesity treatment.