Abstract # 3164 Memory impairment following high-fat diet refeeding is related to caspase-1 activation and oxidative stress in the amygdala

As obesity prevalence increases year-over-year the neurological comorbidities that present with it are increasing as well. Over consumption of calories is a significant causal factor in the development of obesity, and induces a pro-inflammatory state in the brain. Importantly, brain-based IL-1 β appears to be crucial to obesity-related cognitive dysfunction, and several fasting paradigms have been shown to be effective at ameliorating both obesity and IL-1 β -induced cognitive dysfunction. However, these fasting programs can induce binge eating following fasting and it remains unknown whether this type of acute overconsumption can result in negative inflammatory and cognitive sequela. Here, we show that 2hr of high-fat diet (HFD) refeeding reduces novel object recognition (NOR) and novel location recognition (NLR) memory by 13% and 14%, respectively. Additionally, HFD refeeding increases the IL-1 β activating enzyme caspase-1 in the amygdala by ∼ 100%. Calorie intake was significantly correlated with both cognitive performance and caspase-1 activity. Additionally, knockout of either caspase-1 or IL-1 receptor 1 (IL1R1) eliminated recognition memory impairments due to HFD. The antioxidant n-acetylcysteine (NAC; 50 mg/kg) improved NOR and NLR performance by 18% and 14% respectively, and reduced caspase-1 in HFD fed animals by 169%, suggesting a causal role for oxidative stress. Taken together, these data suggest that acute overconsumption during refeeding activates caspase-1 in the amygdala which leads to cognitive impairment via a mechanism mediated by oxidative stress.