Going back on a low-fat diet for just two months, at least in mice, reversed this trend of shrinking cognitive ability as weight begins to normalise, said corresponding author Alexis M Stranahan, from the Medical College of Georgia in the US.
"Microglia eating synapses is contributing to synapse loss and cognitive impairment in obesity," Stranahan said.
The study provides some of the first evidence of why fat is bad for the brain.
Microglia, like macrophages in the body, are known for their ability to ingest trash and infectious agents in the brain, and their highly acidic interior gets rids of it, which helps support the function and health of neurons.
However, as mice get obese, their microglia seem focused on overeating.
"Normally in the brain, microglia are constantly moving around. What happens in obesity is they stop moving," Stranahan said.
"They draw in all their processes; they basically just sit there and start eating synapses. When microglia start eating synapses, the mice don't learn as effectively," Stranahan said.
At four, eight and 12 weeks, the scientists took a series of metabolic measures, such as weight, food intake, insulin and serum glucose levels.
They also measured in the hippocampus, the centre of learning and memory, levels of synaptic markers, proteins found at synapses that correlate with the number of synapses.
They measured levels of inflammatory cytokines, which microglia produce when they start getting activated.
At that point, the research team switched half the mice on the high-fat diet to the low-fat regimen.
It took about two months for their weight to return to normal, although their overall fat pad remained larger than their peers who had never gained weight.
As with most people, the mice that remained on the low-fat diet slowly accumulated a little weight as they aged.
Meanwhile, the group that stayed on the high-fat diet kept getting fatter, more inflamed and losing synapses, she said.
The study was published in the journal Brain, Behaviour, and Immunity.
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