- Study provides novel evidence for the effects of metabolic dysfunctions on brain function using the rat model of metabolic syndrome induced by high fructose intake.
- Study describes that the deleterious consequences of unhealthy dietary habits can be partially counteracted by dietary supplementation of n-3 fatty acid.
- High sugar consumption impaired cognitive abilities and disrupted insulin signalling by engaging molecules associated with energy metabolism and synaptic plasticity; in turn, the presence of docosahexaenoic acid, an n-3 fatty acid, restored metabolic homeostasis.
- These findings expand the concept of metabolic syndrome affecting the brain and provide the mechanistic evidence of how dietary habits can interact to regulate brain functions, which can further alter lifelong susceptibility to the metabolic disorders.
The concept of metabolic syndrome has been mainly associated with the body, and here we introduce this concept with respect to the brain. We provided evidence supporting the harmful impact of the metabolic syndrome on the brain, impacting synaptic plasticity and cognitive function. Our results show the impact of dietary n-3 deficiency on brain function, using a mechanism centred on the action of insulin signalling, energy metabolism and membrane homeostasis. The deficiency of dietary n-3 increases vulnerability to impaired cognitive functions, and intake of a high fructose diet exacerbates this condition. It is encouraging that the presence of the n-3 diet was sufficient to buffer the effects of metabolic dysfunction.
Overall, our results provide mechanistic evidence for how dietary factors can interact to regulate brain plasticity, which can further alter lifelong susceptibility to metabolic disorders. In terms of public health, these results support the encouraging possibility that healthy diets can attenuate the action of unhealthy diets such that the right combination of foods is crucial for a healthy brain.
Proposed mechanism by which insulin resistance leads to disruption of brain metabolism with subsequent effects on synaptic plasticity and cognition. It is also depicted how dietary n-3 fatty acid content in the diet may influence the vulnerability to metabolic dysfunction.
Abundant consumption of fructose leads to an increase in triglyceride and insulin levels in the body, which can affect brain function after crossing the blood–brain barrier. The changes in membrane n-3 and n-6 fatty acids may alter the membrane fluidity, thereby disrupting membrane insulin receptor function. This, in turn, can influence downstream insulin receptor cascades such as IRS-1, Akt and CREB, leading to alteration in synaptic plasticity and cognition. Release of n-6 arachidonic acid from the phospholipid membrane by phospholipase A2 (PLA2) and subsequent peroxidation result in the generation of 4-HNE, which produces alterations in insulin receptor signalling via inhibiting Akt signalling.
These alterations can result in abnormal neuronal signalling, which can reduce learning capacity and other functions that rely on synaptic plasticity and neuronal excitability. Dietary components can also affect mitochondrial energy production by modulating energy molecules LKB1, AMPK and Sir2, which are important for maintaining neuronal excitability and synaptic function via CREB. Regulation of synaptic functions by dietary intervention can also be directly mediated by synapsin I and synaptophysin (SYP).
These events are important for our understanding of how dietary factors can interact to regulate brain plasticity, and how dietary management can be used to promote brain health.