Diet-induced insulin resistance caused blood vessels to become leaky which impaired blood and oxygen flow to a brain region involved in learning and memory (animal evidence).
Obesity and insulin resistance are associated with a leaky blood-brain barrier. This new animal study found that a high-sugar combined with a high-fat diet caused shrinkage of the tight junctions between endothelial cells that make up the blood-brain barrier and actual holes in those cells.
Obesity is known to increase toll-like receptor activation through a variety of mechanisms. One of the mechanisms is through through associated increases of circulating of lipopolysaccharide. Another mechanism is the leaking of fatty acids from fatty acids, triggering toll-like receptors through the recognition of damage-associated molecular patterns (DAMPs). (See “obesity” section of toll-like receptor article.)
However, adenosine, which helps us sleep and helps regulate our blood pressure and is blocked by caffeine may play a role in preventing some of the damaging effects obesity has on the blood-brain barrier, which promotes dementia.
From the article:
They knew that chronic activation of the receptor Adora2a [an adenosine receptor] on the endothelial cells that line this important barrier in our brain can let factors from the blood enter the brain and affect the function of our neurons.
Now Medical College of Georgia scientists have shown that when they block Adora2a in a model of diet-induced obesity, this important barrier function is maintained.
In the brain, adenosine is a neurotransmitter that helps us sleep and helps regulate our blood pressure; in the body it’s also a component of the cell fuel adenosine triphosphate, or ATP. Adenosine also activates receptors Adora1a and Adora2a on endothelial cells, which normally supports healthy relationships between brain activity and blood flow.
Problems arise with chronic activation, particularly in the brain, which is what happens with obesity, says Stranahan.
People who have obesity and diabetes have higher rates of cognitive impairment as they age and most of the related structural changes are in the hippocampus, a center of learning and memory and Stranahan’s focus of study. Fat is a source of inflammation and there is evidence that reducing chronic inflammation in the brain helps prevent obesity-related memory loss.