AgRP mediated calcium Inhibition of feeding via the vagal afferent nerve-brain pathway

Obesity poses serious health risks and is trending younger, developing effective strategies to prevent obesity is crucial. Calcium intake is a potential strategy to reduce weight/fat, as it generally enhances the body's energy metabolism. However, calcium's effects on appetite and its specific mechanisms remain unclear. To investigate these questions, we administered calcium orally to fasted mice and found that calcium inhibited food intake during the first 3 h. Long-term calcium supplementation in water decreased HFD intake, weight gain, and fat deposition while increasing energy metabolism in young mice. Mechanistically, calcium activated the vagal afferent nerves and inhibited ARC^AgRP neurons-key appetite regulation neuron. What's more, these effects are blunted by chemogenetic inhibition of gastrointestinal intestinal vagal afferent nerves or activation of ARC^AgRP neuronal activity. Overall, we showed that ingested calcium activates vagal afferent nerves, inhibiting the activity of ARC^AgRP neurons, thereby reducing food intake. This study supports calcium's role in obesity dietary therapy.