Posted on Nov 07, 2023, 7 p.m.
Obesity has been linked to neurodegenerative disorders like Alzheimer’s disease through insulin resistance in recent research led by the Fred Hutchinson Cancer Research Center published in the journal PLOS Biology. The researchers showed that a high-sugar diet, which is a hallmark of obesity, causes insulin resistance in the brain, which in turn reduces the ability to remove neuronal debris thus increasing the risk of neurodegeneration.
Obesity is already known to be a risk factor for neurodegenerative disorders, but how one leads to the other is less clear. This new study using fruit flies builds on previous research showing that a high-sugar diet leads to insulin resistance in the peripheral organs of the flies, but now focuses on the brain, specifically the glial cells because microglial dysfunction is known to lead to neural degeneration.
According to the researchers, levels of protein P13k indicate how much a cell can respond to insulin, and the team found that a high-sugar diet led to reduced levels, indicating insulin resistance. The team also examined the ensheathing glia (fly equivalent of microglia) which remove neural debris like degenerating axons. These glia were found to have lower levels of the protein Draper indicating impaired function.
Additional testing revealed that the artificial reduction of the levels of P13k led to insulin resistance and low levels of the protein Draper in the ensheathing glia. The team was then able to show that after damaging olfactory neurons, the ensheathing glia was not able to remove the degenerating axons in flies on the high-sugar diet because the levels of Draper proteins did not increase.
The authors wrote that, “Using fruit flies, the authors establish that high-sugar diets trigger insulin resistance in glia, disrupting their ability to clear neuronal debris. This study provides insight into how obesity-inducing diets potentially contribute to the increased risk of neurodegenerative disorders.”
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