The negative effects of obesity can also make their way into the brain and cause memory to decline, according to a new study by researchers from the University of Alabama at Birmingham. The study found that certain epigenetic changes that dysregulate memory-associated genes are associated with chronic obesity - in particular, an enzyme in brain neurons of the hippocampus, a brain structure known to be involved in memory.
Although previous studies have noted memory impairment in obese middle-aged and older people, the underlying molecular mechanisms that caused it were unknown until now. Typically, long-term memory creation stems from changes in DNA methylation and hydroxymethylation, which are the result of epigenetic mechanisms. The current study shows that such epigenetic changes in obese mice are tied to reduced amounts of the SIRT1 gene, which is the main cause of decreased object location spatial memory in obese mice.
"We feel this is a very exciting finding that identifies a new linkage between diet, epigenetics and cognitive function, especially in light of the burgeoning obesity epidemic in the U.S. and elsewhere," David Sweatt, corresponding author of the study, said in a press release, adding that it "offers a novel working model that may serve as a conceptual basis for the development of therapeutic interventions for obesity-induced memory impairment."
Along with the aforementioned SIRT1 gene, the study also found that the expression of three other memory-associated genes, PPARGC1A, PPP1CB and RELN, were also diminished in mice that endured 23 weeks of diet-induced obesity, and the along with SIRT1, PPP1CB and RELN had increased DNA methylation in their gene promotor regions, a sign of decreased gene expression. Furthermore, the SIRT1 promoter showed signs of decreased DNA hydroxymethylation, which is also a sign of decreased gene expression.
When examining the hippocampi of obese mice, the team also found that protein expression of SIRT1 was significantly decreased and one of the enzyme's substrates, acetylated-p53, was significantly increased, which is a sign of reduced enzymatic activity.
All of the above findings took place over the period of weeks, suggesting that obesity-induced memory impairment develops over time. Further studies will need to be conducted to determine if these epigenetic changes are mirrored in obese humans.
The findings were published in the Jan. 27 issue of The Journal of Neuroscience.
