Some research has indicated that a Western diet, which is high in processed foods, sugars, and fats, may be contributing to dementia or cognitive decline. This diet is thought to cause the release of inflammatory molecules that can damage the central nervous system. Neurons are known to express receptors for excitatory or inflammatory molecules that are expressed by fat cells. New research has suggested that the Western diet is promoting a feedback loop that raises the level of oxidants, leading to neurodegeneration. This latest study, which was reported in iScience, has used a mouse model to assess the impact of fat cells on brain function.
In this work, when a mouse model was fed a western diet, there was an increase in the activation of membrane-bound pump called Na,K-ATPase in the brain and peripheral tissues of that model. That was associated with neurodegeneration. Previous work by this team has shown that Na,K-ATPase has an influence on oxidant stress.
The researchers also found that obesity was reduced in mice that were genetically engineered to release a synthetic molecule called NaKtide in their fat cells, which deactivates Na,K-ATPase. The release of that synthetic molecule was also associated with a reversal in the biochemical changes in the brains of these mice that are linked to neurodegeneration, and a reduction in the level of inflammatory cytokines in their circulation. This research has suggested that fat cells can impact cognition and neurodegeneration, and that it could be possible to treat this neurodegeneration by targeting Na,K-ATPase.
“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.
A Western diet can cause oxidant stress and changes in fat due to "Na,K-ATPase signaling which causes systemic inflammation and affects behavioral and brain biochemical changes,” noted first study author Komal Sodhi, M.D., an associate professor of surgery and biomedical sciences at the Joan C. Edwards School of Medicine. With NaKtide, these changes were alleviated and the neurodegeneration improved, added Sodhi.