Findings published last week reveal new insights into the role of fat cells in cognitive decline and neurodegeneration, according to a study that involves the oxidant amplification loop led by Marshall University scientists.
The research, published in iScience, 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,” said senior author Joseph
I Shapiro, M.D., professor and dean of the Marshall University Joan C. Edwards
School of Medicine.
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,” said Komal Sodhi, M.D.,
first author and associate professor of surgery and biomedical sciences at the
Joan C. Edwards School of Medicine. “Our study showed that adipocyte-specific
NaKtide expression in our murine model ameliorated these changes and improved
neurodegenerative phenotype.”
Source: https://www.eurekalert.org/news-releases/932388
Image Credit: Adipose tissue, close-up showing
adipocytes, SEM. David Gregory and
Debbie Marshall. Attribution 4.0
International (CC BY 4.0)
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