New discovery: fat cells play a central role in cognitive decline and neurodegenerative diseases

Written | Edited by xiao xia | Typeset by Wang Duoyu | Hydrographic neurons express receptors for various adipokines, suggesting that the factors released by adipose tissue may directly communicate with the brain
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Alzheimer’s disease is the most common neurodegenerative disease.
Obesity-related metabolic changes and increased inflammation can lead to damage to the central nervous system, leading to neurodeath and changes in neuronal synaptic plasticity, and this metabolic dysfunction increases The risk of developing Alzheimer’s disease
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The Na, K-ATPase signaling pathway in adipocytes is involved in the pathogenesis of a variety of metabolic diseases, and systemic administration of NaKtide can effectively reduce oxidative stress, inflammation and degenerative phenotypes
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However, the role of endogenous NaKtide in obesity and brain disease is still unclear
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Recently, researchers from Marshall University published a research paper titled: Role of Adipocyte Na, K-ATPase Oxidant Amplification Loop in Cognitive Decline and Neurodegeneration in the Cell sub-Journal iScience
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The study showed that fat cells control the systemic response to brain function, leading to impaired memory and cognitive abilities in mice
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The activation of Na,K-ATPase signaling pathway will affect the expression of important protein markers in fat cells and hippocampus, which will deteriorate brain function and lead to neurodegeneration
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Targeting adipocytes against Na,K-ATPase may improve these results.
If this observation is confirmed in humans, adipocyte Na,KATPase may become a clinical target for the treatment of neurodegenerative diseases
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First, the research team constructed transgenic mice that express NaKtide in a tetracycline (TET) dependent manner (TET-On) under the control of the adiponectin promoter
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Doxycycline will activate the adiponectin promoter and specifically overexpress NaKtide polypeptide in adipocytes.
NaKtide inhibits the signal transduction function of Na, K-ATPase
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Compared with mice fed a normal diet, mice fed a Western->
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However, the overexpression of adipocyte-specific NaKtide induced by doxycycline significantly slowed the increase of inflammatory factors, body weight and blood sugar in mice fed Western diet
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By measuring the concentration of NaKtide by ELISA, the research team further confirmed the presence of doxycycline-induced NaKtide expression in visceral adipose tissue
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Studies have shown that reactive oxygen species (ROS) initiate protein carbonylation of the α1 subunit of Na, K-ATPase, followed by phosphorylation of Src, and activate the downstream signal cascade, while regulating extracellular signal-regulated kinase 1/2 (ERK1/2).
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They observed that the protein carbonylation and phosphorylation of Src in the visceral adipose tissue of mice fed Western->
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Next, the research team evaluated the learning and memory abilities of the mice through several cognitive tests
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They observed that the learning ability and memory of mice fed a Western->
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Subsequently, they dissected the brains of the mice and found that in the hippocampus of mice fed on a Western diet, protein carbonylation levels, inflammatory cytokines IL-6 and TNFα levels, and amyloid were significantly increased, which was induced by doxycycline.
Overexpression of NaKtide was weakened
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Finally, in order to study the impact of Western->
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Western->
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In summary, this work found that the overexpression of adipocyte-specific NaKtide peptides in the mouse model improved insulin resistance, inflammation, and neurodegenerative phenotypes, confirming that the Na, K-ATPase signaling pathway of adipocytes can induce the hippocampus of the brain.
The change aspect plays a central role, revealing new insights into the role of fat cells in Alzheimer’s disease
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Link to the paper: https://doi.
org/10.
1016/j.
isci.
2021.
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