A study led by Marshall University scientists this week reveals new insights into the role of fat cells in cognitive decline and neurodegeneration via an oxidant amplification loop. The research, published in iScience, shows that fat cells control the systemic response to brain function, causing impairment in memory and cognition in mice.
“We have aimed to demonstrate that Na, K-ATPase signaling, specifically in adipocytes, plays 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,” said senior author Joseph I Shapiro.
Researchers used a genetically modified mouse model that released the peptide NaKtide specifically in adipocytes 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 the function of the hippocampus, the part of the brain associated with memory and cognition. Inducing oxidative stress through the western diet increased the 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,” said Komal Sodhi, first author. “Our study showed that adipocyte-specific NaKtide expression in our murine model ameliorated these changes and improved neurodegenerative phenotype.”