The impact of the foods we eat on metabolism and cardiac physiology has been studied for decades, yet less is known about the effects of foods on the central nervous system, or the behavioral manifestations that may result from these effects. Previous studies have shown that chronic consumption of high-fat foods leading to diet-induced obesity sensitizes the brain’s inflammatory response to subsequent challenging stimuli, causing deficits in the formation of long-term memories. The new findings reported here demonstrate that acute consumption of a high-fat diet (HFD) produces the same outcomes, thus allowing the examination of mechanisms involved in this process long before obesity and associated co-morbidities occur. Rats fed a HFD for 3 days exhibited increases in corticosterone, the inflammasome-associated protein NLRP3, and the endogenous danger signal HMGB1 in the hippocampus. A low-dose (10μg/kg) lipopolysaccharide (LPS) immune challenge potentiated the neuroinflammatory response in the hippocampus of rats fed the HFD, and caused a deficit in the formation of long-term memory, effects not observed in rats fed regular chow. Blockade of corticosterone action with the glucocorticoid receptor antagonist, mifepristone, prevented the NLRP3 and HMGB1 increases in unchallenged animals, normalized the proinflammatory response to LPS, and prevented the memory impairment. These data suggest that acute HFD consumption increases vulnerability to memory disruptions caused by an immune challenge by upregulating important neuroinflammatory priming and danger signals in the hippocampus, and that these effects are mediated by increases in hippocampal corticosterone.
Significance Statement: American adults consume diets higher in saturated fats and/or refined sugars (HFD) than ever before and these diets have been associated with significant cognitive deficits. This study aims to examine the mechanisms that underlie this relationship. Here, we demonstrate that acute HFD consumption elevates the neuroinflammatory priming signals corticosterone, NLRP3, and HMGB1 in the hippocampus. When followed by an immune challenge, HFD produced a potentiated proinflammatory response and memory deficit. Inhibiting corticosterone signaling during HFD consumption prevented the priming, the potentiated neuroinflammation, and the memory impairment. Together, these data suggest that the glucocorticoid receptor is an important target for attenuating the neuroinflammatory effects associated with HFDs.
The authors report no conflicts of interest.