Calorie Restriction Attenuates Memory Impairment and Reduces Neuroinflammation in Obese Aged Rats

Obesity and aging collectively potentiate inflammatory responses, particularly within the central nervous system. Managing obesity presents a significant challenge, even more so considering the context of aging. Caloric restriction (CR) has been extensively documented in the literature for its multiple health benefits. Motivated by these findings, we hypothesized that CR could serve as a valuable intervention to address the brain alterations and cognitive decline associated with obesity in aged rats. Our investigation revealed that cafeteria diet increased hippocampal and hypothalamic transcripts related to neuroinflammation, along with cognitive deficits determined in the object recognition test in 18-month-old male rats. Western blot data indicate that the obesogenic diet may disrupt the blood-brain barrier and lead to an increase in Toll-like receptor 4 in the hippocampus, events that could contribute to the cognitive deficits observed. Implementing CR after the onset of obesity mitigated neuroinflammatory changes and cognitive impairments. We found that CR increases GABA levels in the hippocampus of aged animals, as demonstrated by liquid chromatography coupled with mass spectrometry analysis. These findings underscore the potential of CR as a therapeutic opportunity to ameliorate the neuroinflammatory and cognitive alterations of obesity, especially in the context of aging.