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J Lipid Res. 2018 Feb;59(2):173-183. doi: 10.1194/jlr.M077222. Epub 2017 Dec 13.

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

Author information

1
Division of Nephrology, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
2
Departments of Statistics, University of Michigan, Ann Arbor, MI 48109.
3
Departments of Pathology, University of Michigan, Ann Arbor, MI 48109.
4
Michigan Regional Comprehensive Metabolomics Resource Core Ann Arbor, MI 48105.
5
Departments of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109.
6
Departments of Neurology, University of Michigan, Ann Arbor, MI 48109.
7
Departments of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109.
8
Departments of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48109.
9
Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.
10
Department of Statistics and Computer and Information Sciences, University of Florida, Gainesville, FL 32611.
11
Division of Nephrology, Departments of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 spennath@umich.edu.

Abstract

Lipids are ubiquitous metabolites with diverse functions; abnormalities in lipid metabolism appear to be 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 coregulated 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 coregulated between plasma and each tissue type in the diabetic mouse. Our results identified several patterns of altered lipid metabolism that may help to identify pathogenic alterations in different tissues and could be used as biomarkers in future research into diabetic microvascular tissue damage.

KEYWORDS:

diabetes; eye; kidney; mass spectrometry; nerve; systems biology

PMID:
29237716
PMCID:
PMC5794414
[Available on 2019-02-01]
DOI:
10.1194/jlr.M077222

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