AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice.

AMP-Activated Protein Kinases / metabolism Animals Diet, High-Fat / adverse effects Eicosanoids / metabolism Kidney Diseases / chemically induced Male Mice Mice, Inbred C57BL
AICAR adenosine 5′-monophosphate adenosine 5′-monophosphate-activated protein kinase chronic kidney disease high-fat diet obesity

Journal

Journal of lipid research
ISSN: 1539-7262
Titre abrégé: J Lipid Res
Pays: United States
ID NLM: 0376606

Informations de publication

Date de publication:
05 2019
Historique:
received: 26 07 2018
revised: 28 02 2019
pubmed: 14 3 2019
medline: 14 8 2020
entrez: 14 3 2019
Statut: ppublish

Résumé

High-fat diet (HFD) causes renal lipotoxicity that is ameliorated with AMP-activated protein kinase (AMPK) activation. Although bioactive eicosanoids increase with HFD and are essential in regulation of renal disease, their role in the inflammatory response to HFD-induced kidney disease and their modulation by AMPK activation remain unexplored. In a mouse model, we explored the effects of HFD on eicosanoid synthesis and the role of AMPK activation in ameliorating these changes. We used targeted lipidomic profiling with quantitative MS to determine PUFA and eicosanoid content in kidneys, urine, and renal arterial and venous circulation. HFD increased phospholipase expression as well as the total and free pro-inflammatory arachidonic acid (AA) and anti-inflammatory DHA in kidneys. Consistent with the parent PUFA levels, the AA- and DHA-derived lipoxygenase (LOX), cytochrome P450, and nonenzymatic degradation (NE) metabolites increased in kidneys with HFD, while EPA-derived LOX and NE metabolites decreased. Conversely, treatment with 5-aminoimidazole-4-carboxamide-1-β-D-furanosyl 5'-monophosphate (AICAR), an AMPK activator, reduced the free AA and DHA content and the DHA-derived metabolites in kidney. Interestingly, kidney and circulating AA, AA metabolites, EPA-derived LOX, and NE metabolites are increased with HFD; whereas, DHA metabolites are increased in kidney in contrast to their decreased circulating levels with HFD. Together, these changes showcase HFD-induced pro- and anti-inflammatory eicosanoid dysregulation and highlight the role of AMPK in correcting HFD-induced dysregulated eicosanoid pathways.

Identifiants

DOI: 10.1194/jlr.M088690 PMID: 30862696 PMC: PMC6495162
pubmed: 30862696
pii: S0022-2275(20)32264-1
doi: 10.1194/jlr.M088690
pmc: PMC6495162
pii:
doi:

Substances chimiques

Eicosanoids 0
AMP-Activated Protein Kinases EC 2.7.11.31

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

937-952

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK089503
Pays : United States
Organisme : NIDDK NIH HHS
ID : F30 DK094532
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK063491
Pays : United States
Organisme : NIDDK NIH HHS
ID : DP3 DK094352
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM020501
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL130944
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK105961
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK082841
Pays : United States

Informations de copyright

Copyright © 2019 Declèves et al.

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Auteurs

Anne-Emilie Declèves (AE)

Institute of Metabolomic Medicine University of California, San Diego, La Jolla, CA; Laboratory of Metabolic and Molecular Biochemistry Faculty of Medicine, Université of Mons, Mons, Belgium. Electronic address: anne-emilie.decleves@umons.ac.be.

Anna V Mathew (AV)

Division of Nephrology Department of Internal Medicine, University of Michigan, Ann Arbor, MI.

Aaron M Armando (AM)

Departments of Pharmacology, University of California, San Diego, La Jolla, CA.

Xianlin Han (X)

Barshop Institute of Aging, Department of Medicine University of Texas Health San Antonio, San Antonio, TX.

Edward A Dennis (EA)

Departments of Pharmacology, University of California, San Diego, La Jolla, CA; Chemistry and Biochemistry University of California, San Diego, La Jolla, CA.

Oswald Quehenberger (O)

Departments of Pharmacology, University of California, San Diego, La Jolla, CA; Medicine, University of California, San Diego, La Jolla, CA.

Kumar Sharma (K)

Institute of Metabolomic Medicine University of California, San Diego, La Jolla, CA; Center for Renal Precision Medicine, Division of Nephrology, Department of Medicine University of Texas Health San Antonio, San Antonio, TX.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › AMP-Activated Protein Kinases › AMP-activated protein kinase activation...
questionsmedicales.fr › Eucaryotes › Animaux › AMP-activated protein kinase activation...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Alimentation riche en graisse › AMP-activated protein kinase activation...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Éicosanoïdes › AMP-activated protein kinase activation...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Maladies du rein › AMP-activated protein kinase activation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › AMP-activated protein kinase activation...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › AMP-activated protein kinase activation...