Fat Cells in Cognitive Decline and Neurodegeneration
Excess visceral fat produces systemic dysfunction throughout the body through many different mechanisms. The most evident is an increase in chronic inflammation, disruptive of health and tissue function. This can occur through a greater burden of senescent cells, through signaling from fat cells that mimics that of infected cells, the presence of debris from dying fat cells, and further mechanisms. Researchers here look at one of these other signaling changes in fat tissue that provoke inflammation, as well as possible means to interfere in that detrimental signaling.
New research shows that fat cells control the systemic response to brain function, causing impairment in memory and cognition in mice. The activation of Na,K-ATPase oxidant amplification loop affects the expression of important protein markers in fat cells as well as in the hippocampus, which can worsen brain function and lead to neurodegeneration. Targeting the fat cells to antagonize Na,K-ATPase may improve these outcomes. "We have aimed to demonstrate that Na,K-ATPase signaling, specifically in adipocytes, play a central role in inducing alterations in specific regions of the brain, most notably in the hippocampus, which is critical to memory and cognitive function."
Researchers used a genetically-modified mouse model that released the peptide NaKtide specifically in adipocytes, or fat cells, to find that NaKtide inhibited the signaling function of Na,K-ATPase. The adipocyte-specific NaKtide expression improved the altered phenotype of adipocytes and improved function of the hippocampus, the part of the brain associated with memory and cognition. Inducing oxidative stress through western diet increased production of inflammatory cytokines confined to adipocytes as well as altered protein markers of memory and cognition in the hippocampus.
"Western diet induces oxidant stress and adipocyte alteration through Na,K-ATPase signaling which causes systemic inflammation and affects behavioral and brain biochemical changes. Our study showed that adipocyte-specific NaKtide expression in our murine model ameliorated these changes and improved neurodegenerative phenotype."