High-fat food reinforces risk taking by suppressing defensive neurons

Palatable food can strongly influence decision-making, often overriding self-preservation instincts. To investigate how high-fat diets (HFD) alter risk-taking behavior, we designed a conflict assay in which mice are tasked with foraging for food under natural predatory threat. While standard diet (SD) food intake decreases in the presence of a rat predator, mice continue to seek and consume HFD despite the threat. This shift in behavior depends on prior HFD exposure and metabolic need, suggesting that post-ingestive experience rather than acute sensory cues drives the preference. Neural recordings revealed that consumption of HFD significantly suppresses cholecystokinin (Cck) escape-triggering neurons in the dorsal premammillary nucleus (PMd), prolonging food seeking even in hazardous conditions. Optogenetic activation of these neurons reduced HFD consumption, whereas their inhibition promoted food seeking under threat, confirming their role in balancing risk and reward. The findings demonstrate that high-energy diets modulate survival-driven behaviors by altering the neural circuits that integrate food reward and danger perception. This work provides mechanistic insight into how dietary factors shape decision-making, with implications for understanding maladaptive eating behaviors in environments where high-calorie foods are abundant despite associated risks.