3 years ago

Shared and distinct lipid-lipid interactions in plasma and affected tissues in a diabetic mouse model.

Kelli M Sas, Hosagrahar V Jagadish, Thekkelnaycke M Rajendiran, Jiahe Lin, Subramaniam Pennathur, Frank C Brosius, Lucy M Hinder, Thomas W Gardner, Eva L Feldman, Tanu Soni, Matthias Kretzler, Steven F Abcouwer, George Michailidis, Viji Nair
Lipids are ubiquitous metabolites with diverse functions; abnormalities in lipid metabolism appear related to complications from multiple diseases, including type 2 diabetes. Through technological advances, the entire lipidome has been characterized, and researchers now need computational approaches to better understand lipid network perturbations in different diseases. Using a mouse model of type 2 diabetes with microvascular complications, we examined lipid levels in plasma and in renal, neural, and retinal tissues to identify shared and distinct lipid abnormalities. We used correlation analysis to construct interaction networks in each tissue, to associate changes in lipids with changes in enzymes of lipid metabolism, and to identify overlap of co-regulated lipid subclasses between plasma and each tissue to define subclasses of plasma lipids to use as surrogates of tissue lipid metabolism. Lipid metabolism alterations were mostly tissue specific in the kidney, nerve and retina; no lipid changes correlated between the plasma and all three tissue types. However, alterations in diacylglycerol and in lipids containing arachidonic acid, an inflammatory mediator, were shared among the tissue types, and the highly saturated cholesterol esters were similarly co-regulated between plasma and each tissue type in the diabetic mouse. Our results identified several patterns of altered lipid metabolism that may help identify pathogenic alterations in different issues and could be used as biomarkers in future research into diabetic microvascular tissue damage.

Publisher URL: http://doi.org/10.1194/jlr.M077222

DOI: 10.1194/jlr.M077222

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