Fight Aging!

It is well known that excess visceral fat tissue is harmful to health over the long term. A sizable amount of this harm stems from mechanisms that act to generate chronic inflammation. These include an accelerated generation of lingering senescent cells, DNA debris from dead fat cells, signaling from normal fat cells that is similar to that secreted by infected cells, and so forth. Researchers here focus on the link between visceral fat and loss of cognitive function, showing that particular inflammatory signal is influential in causing the central nervous system immune cells known as microglia to change their behavior for the worse, thereby harming the function of neurons in the brain. There is a great deal of other evidence pointing towards the importance of inflammatory and senescent microglia in the development of neurodegenerative conditions; chronic inflammation is a noteworthy component of the aging process, and to the extent it can be minimized, such as by maintaining a low level of visceral fat tissue, individuals tend to have a better prognosis.

Scientists have shown one way in which visceral fat is bad for brains is by enabling easy, excessive access for the proinflammatory protein signal interleukin-1 beta. The brain typically does not see much of this interleukin-1 beta, but researchers have found that visceral adiposity generates high, chronic levels of the signal that in turn over-activate the usually protective microglia, the resident immune cells in our brain. A bit like a smoldering pot, this chronic inflammation from visceral fat prompts formation of inflammasome complexes that further amplify the immune response and inflammation. The protein 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, and stokes the inflammation fire. It was known these reactions were causing problems in the body, and now the scientists have evidence they are causing problems in the brain.

To explore brain effects, the scientists knocked NLRP3 out of mice and found the mice were protected against obesity-induced inflammation of the brain and the cognitive problems that can result. They also transplanted visceral adipose tissue from obese mice and obese mice missing NLRP3 into lean mice recipients and found the transplant from the NLRP3 knockout mouse had essentially no effect. But the transplant from the obese but genetically intact mice increased levels of interleukin-1 beta in the hippocampus, a center of learning and memory in the brain, and impaired cognition.

Microglia typically function as watchdogs, constantly surveilling and roaming the brain, eliminating dead cells and other debris as well as a myriad of other tasks like forming and pruning connections between neurons. Microglia also have receptors for interleukin-1 beta, and the protein, whose many actions include promoting inflammation, easily passes through the protective blood brain barrier. Microglia's helpful - or harmful - actions likely result from signals they are exposed to, and another thing interleukin-1 beta appears to do is prompt microglia to wrap around synapses, possibly exerting damaging pressure and/or releasing substances that actually interfere with conversations between neurons. In the absence of disease, microglia also are known to embrace synapses but to release good things like brain-derived neurotrophic factor, which is like fertilizer for these invaluable connections.

Link: https://jagwire.augusta.edu/visceral-fat-delivers-signal-to-the-brain-that-hurts-cognition/