Insulin resistance from high-sugar diets tied to increased neurodegeneration risk

A recent study published in PLOS Biology has shown evidence suggesting a high-sugar diet causes insulin resistance in the brain, lowering the brain's ability to remove neuronal debris, thus increasing neurodegeneration risk.

Neurodegenerative diseases, such as ALS, Parkinson's disease, and Alzheimer's disease affect millions of people worldwide; about 15% of people around the world have a neurodegenerative disease. There is still no clarity on the main cause of many neurodegenerative disorders, but it is known that certain risk factors play a role.

The researchers, using a common fruit fly model, believed a high-sugar diet causes insulin resistance in the brain, lowering the ability of the brain to remove neuronal debris, thus raising neurodegeneration risk.

Using a Drosophila model, the researchers showed that a chronic obesogenic diet induces glial insulin resistance and impedes the clearance of neuronal debris. Specifically, exposure to obesogenic diet downregulates the basal and injury-induced expression of the glia-associated phagocytic receptor, Draper.

Constitutive activation of systemic insulin release from Drosophila insulin-producing cells (IPCs) mimics the effect of diet-induced obesity on glial Draper expression. In contrast, genetically attenuating systemic insulin release from the IPCs rescues diet-induced insulin resistance and Draper expression.

"We drew a causal link between diet-induced obesity and impaired glial phagocytic function, a major contributor to the pathology of age-related neurodegenerative disorders using a Drosophila in vivo model," the researchers wrote.

"Together, our study provides a strong mechanistic insight into how diet-induced obesity modifies glial function, thereby raising neurodegenerative disorder risk," they concluded.

Reference: Alassaf M, Rajan A (2023) Diet-induced glial insulin resistance impairs the clearance of neuronal debris in Drosophila brain. PLoS Biol 21(11): e3002359. https://doi.org/10.1371/journal.pbio.3002359