How Obesity May Impair Memory

Researchers uncover a molecular link between obesity and memory deficits in mice—as well as a potential treatment

It’s no secret that obesity, which plagues more than 600 million people worldwide—more than one in three adults in the U.S. alone—leads to serious health problems: cardiovascular disease, diabetes and even several types of cancer. But obesity has also been established as a risk factor for cognitive decline, particularly in middle-aged and older people.
What’s not as well understood is this link’s underlying molecular mechanism—and that’s exactly what a group of researchers at the University of Alabama at Birmingham sought to decipher in a four-part experiment on mice published last month in The Journal of Neuroscience.
First, the researchers studied behavior in healthy and obese mice during memory tasks involving object recognition and location. Much like previous research from other groups, the Alabama team found that compared with their healthy counterparts, the overweight mice performed poorly on a spatial memory task, which relies on the brain’s hippocampus.
Next, the researchers took a look at epigenetic differences in the hippocampi of healthy and obese mice—in other words, at whether environmental factors, in this case obesity, may have influenced the expression of genes in the hippocampus in either group of mice. Using a molecular purification technique to isolate for and analyze methylated DNA sequences (which are associated with gene suppression), the team confirmed that four genes associated with memory formation were not expressed as strongly in the obese mice—suggesting that their obesity had somehow influenced how cells “read” these genes. “One of the particularly exciting things is that this finding links two hot areas of neuroscience: epigenetic mechanisms and cognitive effects of obesity,” says David Sweatt, a neurobiologist at Alabama and study co-author.
One gene in particular, Sirtuin 1 (Sirt1), showed further epigenetic changes that were not observed in the other three genes. “This meant that Sirt1 could lie at the nexus of metabolic dysfunction and memory formation,” says lead author Frankie Heyward, a graduate student in Sweatt’s laboratory. “We were the first to explicitly implicate reduced Sirt1 and increased Sirt1 DNA methylation in the etiology of obesity-induced memory impairment.”