Long-term adherence to dietary interventions remains a major challenge in the management of overweight and obesity. Feeding behavior is regulated by homeostatic mechanisms within hypothalamic circuits and hedonic-motivational processes mediated by mesocorticolimbic pathways. These systems are influenced by neuroendocrine signals, inflammatory status, and metabolic cues that shape appetite and reward-driven eating. Among nutritional factors, the balance between omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) has emerged as a key modulator of these processes. This mini-review examines how PUFA balance influences hypothalamic energy homeostasis regulation, enteroendocrine signaling, reward circuits, and gut microbiota. A high omega-6/omega-3 ratio promotes inflammation, enhances endocannabinoid signaling, impairs insulin sensitivity, and increases reward-driven feeding. Conversely, increasing omega-3 availability shifts PUFA balance toward anti-inflammatory states, improves metabolic and satiety signaling, and reduces the drive to eat. Circulating fatty acid profiles provide objective indicators of dietary intake and may help assess adherence to dietary patterns. The evidence reviewed here provides a biological framework supporting a potential link between dietary fatty acid composition and long-term adherence, warranting further investigation.
Pipicelli et al. (2026) studied this question.