Peripheral adipose tissue insulin resistance alters lipid composition and function of hippocampal synapses.

Abstract:

:Compelling evidence indicates that type 2 diabetes mellitus, insulin resistance (IR), and metabolic syndrome are often accompanied by cognitive impairment. However, the mechanistic link between these metabolic abnormalities and CNS dysfunction requires further investigations. Here, we evaluated whether adipose tissue IR and related metabolic alterations resulted in CNS changes by studying synapse lipid composition and function in the adipocyte-specific ecto-nucleotide pyrophosphate phosphodiesterase over-expressing transgenic (AtENPP1-Tg) mouse, a model characterized by white adipocyte IR, systemic IR, and ectopic fat deposition. When fed a high-fat diet, AtENPP1-Tg mice recapitulate essential features of the human metabolic syndrome, making them an ideal model to characterize peripherally induced CNS deficits. Using a combination of gas chromatography and western blot analysis, we found evidence of altered lipid composition, including decreased phospholipids and increased triglycerides (TG) and free fatty acid in hippocampal synaptosomes isolated from high-fat diet-fed AtENPP1-Tg mice. These changes were associated with impaired basal synaptic transmission at the Schaffer collaterals to hippocampal cornu ammonis 1 (CA1) synapses, decreased phosphorylation of the GluN1 glutamate receptor subunit, down-regulation of insulin receptor expression, and up-regulation of the free fatty acid receptor 1.

journal_name

J Neurochem

authors

Sallam HS,Tumurbaatar B,Zhang WR,Tuvdendorj D,Chandalia M,Tempia F,Laezza F,Taglialatela G,Abate N

doi

10.1111/jnc.13043

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

125-33

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

133

pub_type

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