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- Publisher Website: 10.1016/j.bbadis.2017.04.006
- Scopus: eid_2-s2.0-85021242639
- PMID: 28396286
- WOS: WOS:000407657200001
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Article: Altered mitochondrial and peroxisomal integrity in lipocalin-2-deficient mice with hepatic steatosis
Title | Altered mitochondrial and peroxisomal integrity in lipocalin-2-deficient mice with hepatic steatosis |
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Authors | |
Keywords | GO analysis Peroxisomes Liver Mitochondria Proteomics Phosphoinositide (3,4,5) triphosphate Dietary model Lipidomics Iron pool Fatty acid binding proteins Arachidonic acid |
Issue Date | 2017 |
Citation | Biochimica et Biophysica Acta - Molecular Basis of Disease, 2017, v. 1863, n. 9, p. 2093-2110 How to Cite? |
Abstract | © 2017 Elsevier B.V. Lipocalin-2 (LCN2) is a secreted adipokine that transports small hydrophobic molecules such as fatty acids and steroids. LCN2 limits bacterial growth by sequestering iron-containing siderophores and in mammalian liver protects against inflammation, infection, injury and other stressors. Because LCN2 modulates hepatic fat metabolism and homeostasis, we performed a comparative profiling of 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 revealed differential expression of BRIT1/MCPH1, FABP5, HMGB1, HBB2, and L-FABP, results confirmed by Western blotting. Gene ontology enrichment analysis identified enrichment for genes associated with mitochondrial membrane permeabilization and metabolic processes involving carboxylic acid. Measurements of mitochondrial membrane potential, mitochondrial chelatable iron pool, intracellular lipid peroxidation, and peroxisome numbers in primary hepatocytes confirmed that LCN2 regulates mitochondrial and peroxisomal integrity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry imaging identified significant changes to sphingomyelins, triglycerides, and glycerophospholipids in livers of mice fed an MCD diet regardless of LCN2 status. However, two arachidonic acid-containing glycerophospholipids were increased in Lcn2-deficient livers. Thus, LCN2 influences peroxisomal and mitochondrial biology in the liver to maintain triglyceride balance, handle oxidative stress, and control apoptosis. |
Persistent Identifier | http://hdl.handle.net/10722/293021 |
ISSN | 2023 Impact Factor: 4.2 2023 SCImago Journal Rankings: 1.580 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Asimakopoulou, Anastasia | - |
dc.contributor.author | Fülöp, Annabelle | - |
dc.contributor.author | Borkham-Kamphorst, Erawan | - |
dc.contributor.author | de Leur, Eddy Van | - |
dc.contributor.author | Gassler, Nikolaus | - |
dc.contributor.author | Berger, Thorsten | - |
dc.contributor.author | Beine, Birte | - |
dc.contributor.author | Meyer, Helmut E. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Hopf, Carsten | - |
dc.contributor.author | Henkel, Corinna | - |
dc.contributor.author | Weiskirchen, Ralf | - |
dc.date.accessioned | 2020-11-17T14:57:42Z | - |
dc.date.available | 2020-11-17T14:57:42Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Biochimica et Biophysica Acta - Molecular Basis of Disease, 2017, v. 1863, n. 9, p. 2093-2110 | - |
dc.identifier.issn | 0925-4439 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293021 | - |
dc.description.abstract | © 2017 Elsevier B.V. Lipocalin-2 (LCN2) is a secreted adipokine that transports small hydrophobic molecules such as fatty acids and steroids. LCN2 limits bacterial growth by sequestering iron-containing siderophores and in mammalian liver protects against inflammation, infection, injury and other stressors. Because LCN2 modulates hepatic fat metabolism and homeostasis, we performed a comparative profiling of 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 revealed differential expression of BRIT1/MCPH1, FABP5, HMGB1, HBB2, and L-FABP, results confirmed by Western blotting. Gene ontology enrichment analysis identified enrichment for genes associated with mitochondrial membrane permeabilization and metabolic processes involving carboxylic acid. Measurements of mitochondrial membrane potential, mitochondrial chelatable iron pool, intracellular lipid peroxidation, and peroxisome numbers in primary hepatocytes confirmed that LCN2 regulates mitochondrial and peroxisomal integrity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry imaging identified significant changes to sphingomyelins, triglycerides, and glycerophospholipids in livers of mice fed an MCD diet regardless of LCN2 status. However, two arachidonic acid-containing glycerophospholipids were increased in Lcn2-deficient livers. Thus, LCN2 influences peroxisomal and mitochondrial biology in the liver to maintain triglyceride balance, handle oxidative stress, and control apoptosis. | - |
dc.language | eng | - |
dc.relation.ispartof | Biochimica et Biophysica Acta - Molecular Basis of Disease | - |
dc.subject | GO analysis | - |
dc.subject | Peroxisomes | - |
dc.subject | Liver | - |
dc.subject | Mitochondria | - |
dc.subject | Proteomics | - |
dc.subject | Phosphoinositide (3,4,5) triphosphate | - |
dc.subject | Dietary model | - |
dc.subject | Lipidomics | - |
dc.subject | Iron pool | - |
dc.subject | Fatty acid binding proteins | - |
dc.subject | Arachidonic acid | - |
dc.title | Altered mitochondrial and peroxisomal integrity in lipocalin-2-deficient mice with hepatic steatosis | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1016/j.bbadis.2017.04.006 | - |
dc.identifier.pmid | 28396286 | - |
dc.identifier.scopus | eid_2-s2.0-85021242639 | - |
dc.identifier.volume | 1863 | - |
dc.identifier.issue | 9 | - |
dc.identifier.spage | 2093 | - |
dc.identifier.epage | 2110 | - |
dc.identifier.eissn | 1879-260X | - |
dc.identifier.isi | WOS:000407657200001 | - |
dc.identifier.issnl | 0925-4439 | - |