The “healthy gut, healthy brain” concept is central to functional and integrative medicine. Revisiting a widely discussed topic from a different perspective, Dr Stranahan & team show that excessive weight around the waist can trigger processes contributing to cognitive decline .
We discuss the results of their recently published study, identifying a mechanism in mice suggesting causation instead of relying on correlation.
Visceral adiposity, or carrying excessive weight our waists can trigger a strong signal to our brain’s immune cells that turns them against us. This unleashes inflammation that damages cognition, according to scientists.
A study by researchers at the Medical College of Georgia have for the first time established a biological link between between excessive visceral fat and neuroinflammation. To date, researchers had only observed a correlation between the two.
In technical terms, excessive visceral fat enables easier and excessive access for the protein signal interleukin-1 beta. This protein triggers microglia (the brain’s “helper/watchdog” cells) to turn hostile to well-functioning synapses, damaging them and contributing to cognitive decline. The brain typically does not see much of interleukin 1-beta proteins, but it was observed that visceral adiposity chronically elevated its levels, turning the microglia over-active.
The study was performed on mice, some of whom had their NLRP3 proteins removed (NLRP3 is a protein that promotes the production and release of interleukin 1-beta in fat cells and contributes to inflammation). The researchers observed that the mice without the NLRP3 protein were protected from obesity-induced inflammation. The results were verified through transplantation of visceral tissue.
To assess the cognitive impact, the mice were assessed in their ability to solve a water maze after 12 weeks on a high- or low-fat diet. Mice with the interleukin 1-beta receptor switched off performed significantly better. These mice also recognised new objects to play with better and showed stronger synapses.
It is commonly known that increased rates of cognitive decline have been linked to obesity in humans, including the shrinkage of crucial parts of the brain like the hippocampus.
The research was funded by the National Institutes of Health.
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 Guo DH, Yamamoto M, Hernandez CM, Khodadadi H, Baban B, Stranahan AM. Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells. J Clin Invest. 2020;
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