Lipocalin-2 (LCN2) is a small secreted adipokine that binds and transports small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores. In mammalian liver, LCN2 protects against inflammation, infection, injury and other forms of cellular stress. Because previous work indicated that LCN2 is a key modulator of hepatic fat metabolism and homeostasis, we performed a comparative profiling of the proteins and lipids of wild type (WT) and Lcn2-deficient mice fed either standard chow or a methionine- and choline-deficient (MCD) diet. Label-free proteomics and 2D-DIGE protein expression profiling identified differential expression of BRIT1/MCPH1, FABP5, HMGB1, HBB2, and L-FABP, results confirmed by Western blotting.
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Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry imaging revealed altered spatial distribution of many lipids in tissue sections of Lcn2-deficient mice or WT mice fed an MCD diet. Significant changes to m/z signal intensities for various sphingomyelins, triglycerides, and glycerophospholipid species were observed, including elevations of phosphatidylinositol diphosphates and -triphosphates in MCD-fed mice, regardless of LCN2 status. Interestingly, two arachidonic acid containing glycerophospholipids were increased in Lcn2-deficient livers, suggesting that LCN2 loss interferes with arachidonic acid metabolism. Lastly, measurements on mitochondrial membrane potential, mitochondrial chelatable iron pool, intracellular lipid peroxidation, and peroxisome staining showed that the presence of LCN2 impacts mitochondrial and peroxisome integrity and function in primary
Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry imaging revealed altered spatial distribution of many lipids in tissue sections of Lcn2-deficient mice or WT mice fed an MCD diet. Significant changes to m/z signal intensities for various sphingomyelins, triglycerides, and glycerophospholipid species were observed, including elevations of phosphatidylinositol diphosphates and -triphosphates in MCD-fed mice, regardless of LCN2 status. Interestingly, two arachidonic acid containing glycerophospholipids were increased in Lcn2-deficient livers, suggesting that LCN2 loss interferes with arachidonic acid metabolism. Lastly, measurements on mitochondrial membrane potential, mitochondrial chelatable iron pool, intracellular lipid peroxidation, and peroxisome staining showed that the presence of LCN2 impacts mitochondrial and peroxisome integrity and function in primary