Researchers find weight gain induced by a high-fat diet may destroy synapses in the brain, impairing cognitive functioning.
Published in the journal Brain, Behavior and Immunity, the study suggests a high-fat diet destroys synapses - connections that aid communication between neurons, or brain cells - in the hippocampus of the brain, which may impair learning and memory.
But it is not all bad news; the research also suggests that switching to a low-fat diet for 2 months can counteract the brain-damaging effects of a high-fat diet.
High-fat diets are a main contributor to obesity, which has become a major public health concern in the US. More than a third of adults in the US are obese, meaning they are at greater risk of heart disease, stroke, type 2 diabetes and some types of cancer.
Aside from weight gain, however, there is increasing evidence that a high-fat diet can harm the brain. The researchers at the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Georgia Regents University decided to investigate this association further.
Brain effects of high- and low-fat diets compared in mice
To reach their findings, the research team randomized male mice to one of two diet groups: one group was fed a diet in which around 10% of calories came from saturated fat, while the other group was fed chow that contained 60% fat.
According to the researchers, the diets the mice were fed represented a healthy diet versus a fast-food diet in humans. Each diet contained similar amounts macronutrients and protein, the team notes.
The weight, food intake, insulin levels and blood glucose levels of the mice were assessed at 4, 8 and 12 weeks after diet initiation.
Additionally, the researchers analyzed the hippocampi of the mice - the brain region associated with learning and memory. Specifically, they measured levels of synaptic markers in the hippocampus - proteins that represent the number of synapses in the brain - and cytokine levels, which are markers of inflammation.
Excess fat triggers autoimmune response that destroys synapses
At 4 and 8 weeks, the team found the levels of synaptic markers were the same for both groups of mice, though the mice on a high-fat diet had gained weight.
Fast facts about obesity
- Around 17% of children and teenagers aged 2-19 in the US are obese
- An adult is defined as obese if they have a body mass index (BMI) of 30 or more
- The medical cost of obesity in the US totals around $147 billion a year.
By 12 weeks, however, the mice fed a high-fat diet had not only become obese, but they also had reduced levels of synaptic markers and increased cytokine levels, indicating that synapses were being destroyed in the hippocampus.
The researchers explain that when there is too much fat in the body, this leads to chronic inflammation, triggering an autoimmune response from microglia - glial cells that form the primary immune defense in the central nervous system.
Microglia usually help rid the brain of harmful agents, which helps to protect and strengthen neurons, but it appears that too much fat in the body impairs this process.
Normally in the brain, microglia are constantly moving around. They are always moving around their little fingers and processes. What happens in obesity is they stop moving. 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.
Switching to low-fat diet reversed synaptic loss and function
Next, the research team swapped half of the mice on the high-fat diet to the low-fat diet to see how this affected their brains.
They found that the weight of these mice returned to normal within around 2 months, though they did have a larger "fat pad" - a layer of fat that simplifies future weight gain - than mice fed a low-fat diet that did not gain weight.
What is more, while the mice that remained on the high-fat diet continued to gain weight, experience more inflammation and lose more synapses, synaptic loss and function were restored among those that switched to the low-fat diet. This suggests swapping to a low-fat diet may offset neurological damage caused by a high-fat diet.
"Microglia eating synapses is contributing to synapse loss and cognitive impairment in obesity. On the one hand, that is very scary, but it's also reversible, meaning that if you go back on a low-fat diet that does not even completely wipe out the adiposity, you can completely reverse these cellular processes in the brain and maintain cognition."
The research team notes that the findings suggest medications currently used to treat Crohn's disease and rheumatoid arthritis - which work by blocking certain inflammatory cytokines, some of which were present in the brains of mice fed a high-fat diet - may show promise for neurological conditions involving synaptic loss, though further research is required.
In the meantime, if you have overindulged these past few days, think about eating a bit healthier - your brain may thank you for it.
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