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2019-05-05 - Article/Dans un journal avec peer-review - Anglais - 15 page(s)

Decleves Anne-Emilie , Mathew AV, Armando AM, Han X, Dennis EA, Quehenberger O, Sharma K, "AMP-activated protein kinase activation ameliorates eicosanoid dysregulation" in Journal of Lipid Research, 60, 5, 937-952, doi: 10.1194/jlr.M088690.

  • Edition : Lipid Research (MD)
  • Codes CREF : Biochimie (DI3112), Néphrologie - urologie (DI3325), Diabétologie (DI3373), Métabolisme (DI3223), Lipides, steroides, membranes (DI311C)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Centre de Recherche UMONS-Ambroise Paré (UMHAP)
Texte intégral :

Abstract(s) :

(Anglais) Send to J Lipid Res. 2019 May;60(5):937-952. doi: 10.1194/jlr.M088690. Epub 2019 Mar 12. AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice. Declèves AE1,2, Mathew AV3, Armando AM4, Han X5, Dennis EA4,6, Quehenberger O4,7, Sharma K8,9. Author information 1Institute of Metabolomic Medicine University of California, San Diego, La Jolla, CA anne-emilie.decleves@umons.ac.be.2Laboratory of Metabolic and Molecular Biochemistry Faculty of Medicine, Université of Mons, Mons, Belgium.3Division of Nephrology Department of Internal Medicine, University of Michigan, Ann Arbor, MI.4Departments of Pharmacology, University of California, San Diego, La Jolla, CA.5Barshop Institute of Aging, Department of Medicine University of Texas Health San Antonio, San Antonio, TX.6Chemistry and Biochemistry University of California, San Diego, La Jolla, CA.7Medicine, University of California, San Diego, La Jolla, CA.8Institute of Metabolomic Medicine University of California, San Diego, La Jolla, CA.9Center for Renal Precision Medicine, Division of Nephrology, Department of Medicine University of Texas Health San Antonio, San Antonio, TX. Abstract 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. Copyright © 2019 Declèves et al.

Identifiants :
  • DOI : 10.1194/jlr.M088690