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Metabolic syndrome in the brain: Deficiency in omega-3-fatty acid exacerbates dysfunctions in insulin receptor signaling and cognition

Agrawal R, Gomez-Pinilla F (2012) J Physiol 590(Pt 10): 2485-99. doi: 10.1113/jphysiol.2012.230078. Epub 2012 Apr 2. 

Web URL: View this and related abstracts via PubMed here. Free full text is available online.

Abstract:

We pursued studies to determine the effects of the metabolic syndrome (MetS) in brain, and the possibilities to modulate these effects by dietary interventions. In addition, we have assessed potential mechanisms by which brain metabolic disorders can impact synaptic plasticity and cognition. We report that high-dietary fructose consumption leads to increase in insulin resistance index, insulin and triglyceride levels, which characterize MetS.

Rats fed on an n-3 deficient diet showed memory deficits in Barnes Maze, which were further exacerbated by fructose intake. In turn, n-3 deficient diet and fructose interventions disrupted insulin receptor signaling in hippocampus as evidenced by a decrease in phosphorylation of insulin receptor and its downstream effector Akt.

We found that high fructose consumption with n-3 deficient diet disrupts membrane homeostasis as evidenced by an increase in the ratio of n-6/n-3 fatty acids and levels of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation. Disturbances in brain energy metabolism due to n-3 deficiency and fructose treatments were evidenced by a significant decrease in AMPK phosphorylation and its upstream modulator LKB1 as well as a decrease in Sir2 levels. The decrease in phosphorylation of CREB, synapsin I and synaptophysin (SYP) levels by n-3 deficiency and fructose shows the impact of metabolic dysfunction on synaptic plasticity.

All parameters of metabolic dysfunction related to the fructose treatment were ameliorated by the presence of dietary n-3 fatty acid.

Results showed that dietary n-3 fatty acid deficiency elevates the vulnerability to metabolic dysfunction and impaired cognitive functions by modulating insulin receptor signaling and synaptic plasticity.

FAB RESEARCH COMMENT:

For an accessible summary of this research and its implications, see the associated news article: 



And for an excellent review of the interactions between dietary intakes of fructose and omega-3 fatty acids, see also