Insulin could be the key to the link between obesity and the risk of developing dementia. A new study suggests that a high-sugar diet may lead to insulin resistance in the brain, potentially increasing the risk of neurodegenerative diseases such as Alzheimer’s.
On one hand, it has been demonstrated that obesity increases the risk of developing neurodegenerative disorders such as Alzheimer’s disease, but the precise mechanisms of this connection are not known. However, the overconsumption of sugary foods is the primary cause of obesity and its complications. On the other hand, certain epidemiological studies conducted in humans establish a link between poor dietary habits and the risk of developing Alzheimer’s disease by altering our brains.
The Choice of the Fruit Fly
A new study published in the journal PLOS Biology explains the mechanisms by which diets that promote obesity could contribute to an increased risk of developing a neurodegenerative disorder. Research conducted on fruit flies, a type of small fruit fly, suggests that insulin resistance induced by a high-sugar diet can disrupt the ability of the brain’s glial cells to eliminate neuronal debris. This process is crucial to preventing neurodegeneration.
The selection of the fruit fly as the subject of study was not arbitrary. Indeed, this fly consumes sugar from fruits, and there are physiological similarities between this species and humans. “We find that when we feed flies a high-sugar diet, it triggers remarkable physiological changes that mirror the effects of type 2 diabetes in humans including insulin resistance,” explained researcher Akhila Rajan to New Atlas. Therefore, fruit flies subjected to a high-sugar diet serve as an excellent model for understanding what goes wrong in humans.
Promising Results for Humans
Researchers first showed that a high-sugar diet caused insulin resistance in the flies’ peripheral organs, and then it appeared in their brains. They specifically investigated glial cells due to their role in neuronal degeneration. The study revealed that insulin resistance reduces levels of PI3k and Draper proteins in glial cells, hindering their function in clearing neuronal debris. The highlighted phenomenon is phagocytosis, a crucial cellular mechanism for eliminating pathogens and dead or dysfunctional particles. It is commonly accepted that dementia-related diseases (such as Alzheimer’s) are characterized by the brain’s inability to eliminate toxic proteins (amyloid proteins in the case of Alzheimer’s).
These findings present new perspectives on preventive therapies for Alzheimer’s disease, such as increasing circulating insulin levels. A recent phase 2 clinical trial tested an intranasal insulin spray designed to deliver the hormone directly to the brain, potentially improving cognitive health. Initial results were deemed “slightly promising.”
In summary, while there are valid reasons to believe that insulin signaling alteration plays a role in Alzheimer’s disease development, a deeper understanding is needed to elucidate how the findings in Drosophila translate to humans.