MicroRNA-33 (miR-33) regulates hunger signaling in hypothalamic AgRP neurons. Loss of miR-33 in AgRP neurons leads to increased feeding, obesity, and metabolic dysfunction in mice. miR-33 targets genes involved in mitochondrial biogenesis and fatty acid metabolism, influencing AgRP neuron activity. miR-33 deficiency promotes obesity and metabolic disorders by increasing food intake and altering glucose and lipid homeostasis. miR-33 also affects mitochondrial density and function in AgRP neurons, enhancing their activity. miR-33 plays a critical role in suppressing AgRP neuron activity, thereby limiting hunger signals and preventing obesity. miR-33 is involved in lipid metabolism and energy homeostasis, and its regulation is linked to the function of AgRP neurons. Targeting miR-33 in AgRP neurons could provide new therapeutic approaches for modulating feeding behavior and metabolic diseases. The study highlights the importance of miR-33 in controlling feeding behavior and metabolic processes, suggesting potential applications in treating obesity and related conditions. The findings demonstrate that miR-33 is a key regulator of AgRP neuron activity, influencing hunger signals and metabolic homeostasis. The study also shows that miR-33 deficiency in AgRP neurons leads to increased food consumption, weight gain, and metabolic dysfunction, indicating its role in maintaining energy balance. The research provides insights into the molecular mechanisms underlying hunger signaling and metabolic regulation, offering potential targets for therapeutic interventions.MicroRNA-33 (miR-33) regulates hunger signaling in hypothalamic AgRP neurons. Loss of miR-33 in AgRP neurons leads to increased feeding, obesity, and metabolic dysfunction in mice. miR-33 targets genes involved in mitochondrial biogenesis and fatty acid metabolism, influencing AgRP neuron activity. miR-33 deficiency promotes obesity and metabolic disorders by increasing food intake and altering glucose and lipid homeostasis. miR-33 also affects mitochondrial density and function in AgRP neurons, enhancing their activity. miR-33 plays a critical role in suppressing AgRP neuron activity, thereby limiting hunger signals and preventing obesity. miR-33 is involved in lipid metabolism and energy homeostasis, and its regulation is linked to the function of AgRP neurons. Targeting miR-33 in AgRP neurons could provide new therapeutic approaches for modulating feeding behavior and metabolic diseases. The study highlights the importance of miR-33 in controlling feeding behavior and metabolic processes, suggesting potential applications in treating obesity and related conditions. The findings demonstrate that miR-33 is a key regulator of AgRP neuron activity, influencing hunger signals and metabolic homeostasis. The study also shows that miR-33 deficiency in AgRP neurons leads to increased food consumption, weight gain, and metabolic dysfunction, indicating its role in maintaining energy balance. The research provides insights into the molecular mechanisms underlying hunger signaling and metabolic regulation, offering potential targets for therapeutic interventions.