title: Effect of dietary krill oil supplementation on the endocannabinoidome of metabolically relevant tissues from high-fat-fed mice.
abstract: BACKGROUND
  Omega-3 polyunsaturated fatty acids (ω-3-PUFA) are known to ameliorate several metabolic risk factors for cardiovascular disease, and an association between elevated peripheral levels of endogenous ligands of cannabinoid receptors (endocannabinoids) and the metabolic syndrome has been reported. We investigated the dose-dependent effects of dietary ω-3-PUFA supplementation, given as krill oil (KO), on metabolic parameters in high fat diet (HFD)-fed mice and, in parallel, on the levels, in inguinal and epididymal adipose tissue (AT), liver, gastrocnemius muscle, kidneys and heart, of: 1) the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), 2) two anandamide congeners which activate PPARα but not cannabinoid receptors, N-oleoylethanolamine and N-palmitoylethanolamine, and 3) the direct biosynthetic precursors of these compounds.
  
  
  METHODS
  Lipids were identified and quantified using liquid chromatography coupled to atmospheric pressure chemical ionization single quadrupole mass spectrometry (LC-APCI-MS) or high resolution ion trap-time of flight mass spectrometry (LC-IT-ToF-MS).
  
  
  RESULTS
  Eight-week HFD increased endocannabinoid levels in all tissues except the liver and epididymal AT, and KO reduced anandamide and/or 2-AG levels in all tissues but not in the liver, usually in a dose-dependent manner. Levels of endocannabinoid precursors were also generally down-regulated, indicating that KO affects levels of endocannabinoids in part by reducing the availability of their biosynthetic precursors. Usually smaller effects were found of KO on OEA and PEA levels.
  
  
  CONCLUSIONS
  Our data suggest that KO may promote therapeutic benefit by reducing endocannabinoid precursor availability and hence endocannabinoid biosynthesis.
authors.affiliation: Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, CNR, Pozzuoli (NA), Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Dipartimento di Biologia Sperimentale, Università di Cagliari, Italy; and Nutrisearch s.r.l. Pula (CA) Italy.
authors.forename: Gianfranca
authors.initials: G
authors.lastname: Carta
authors.affiliation: Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, CNR, Pozzuoli (NA), Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.affiliation: Dipartimento di Biologia Sperimentale, Università di Cagliari, Italy; and Nutrisearch s.r.l. Pula (CA) Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Murru
authors.affiliation: Dipartimento di Biologia Sperimentale, Università di Cagliari, Italy; and Nutrisearch s.r.l. Pula (CA) Italy.
authors.forename: Lina
authors.initials: L
authors.lastname: Cordeddu
authors.affiliation: Aker BioMarine ASA, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Berge
authors.affiliation: Nutrition and Metabolism Group, Heart Research Institute, Sydney, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: Tandy
authors.affiliation: Nutrition and Metabolism Group, Heart Research Institute, Sydney, Australia.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Cohn
authors.affiliation: Clanet Oy, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Griinari
authors.affiliation: Dipartimento di Biologia Sperimentale, Università di Cagliari, Italy; and Nutrisearch s.r.l. Pula (CA) Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Banni
authors.affiliation: Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, CNR, Pozzuoli (NA), Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo