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Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats
Mechanisms Underlying Diet-Induced Cognitive Decline in Older Adults
Metabolic syndrome and obesity are important public health problems associated with aging-related cognitive impairment. Previous research from Butler et al. has shown that consuming a high-fat diet (HFD) for a short period can quickly impair memory through a neuroinflammatory process. However, whether these rapid inflammatory effects are exclusive to the brain remains unclear. Additionally, alterations in gut microbiome composition have been associated with obesity and cognitive dysfunction. However, the interaction between diet, aging, and gut microbiome changes, particularly how quickly these shifts occur, needs further investigation. Butler et al. (2025) examined the effects of HFD after two distinct durations: three months (to simulate diet-induced obesity) and three days (to observe immediate dietary impacts) on memory function, anxiety-related behavior, central and peripheral inflammation, and gut microbiome composition in both young and aged rats. The findings demonstrated that, in older rats, but not in younger ones, both short-term and long-term HFD intake resulted in memory deficits and an increase in anxiety-like behavior. Imbalances in pro- and anti-inflammatory cytokines in the hippocampal and amygdala of elderly rats on an HFD at both time periods were linked to these behavioral consequences. However, peripheral inflammation and changes in fasting glucose and insulin levels in the distal colon and visceral adipose tissue were observed only after long-term HFD consumption in both young and aged rats. Furthermore, while minor HFD-induced modifications in the gut microbiome occurred rapidly, substantial age-related effects were only evident following extended HFD exposure. These findings suggest that neuroinflammation, cognitive decline, and anxiety-like behavior due to an HFD in aging occur faster and independently of the peripheral markers of diet-induced obesity. [NPID: Cytokines, high-fat diet, gut microbiome]
Year: 2025
