A mouse study explains why excessive weight around our middle affects cognition. It seems that such fat, known as visceral adiposity, generates high, chronic levels of a signal that encourages the formation of inflammasome complexes that amplify the immune response and inflammation.

A protein called NLRP3 is a core component of the inflammasome complex in the fat, and it’s what promotes the production and release of interleukin-1 beta by fat cells. When NLRP3 was blocked in mice, they became protected against such inflammation and cognitive problems. When visceral adipose tissue from obese mice and obese mice missing NLRP3 was transplanted into lean mice, the tissue from those missing NLRP3 had no deleterious effect, but the tissue from the intact obese mice caused increased levels of interleukin-1 beta in the hippocampus, and impaired cognition.

Mice missing interleukin-1 beta’s receptor on the microglia were also protected.

There are indications that interleukin-1 beta also prompts microglia to wrap around synapses, potentially interfering with the communication between neurons.

https://www.eurekalert.org/pub_releases/2020-03/mcog-vfd030220.php

Guo, D.-H., Yamamoto, M., Hernandez, C. M., Khodadadi, H., Baban, B., & Stranahan, A. M. (2020). Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1⁺ cells. The Journal of Clinical Investigation, 130(4), 1961–1976. https://doi.org/10.1172/JCI126078