Fish oil and inflammatory status alter the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes in mouse plasma and tissues

M.G.J. Balvers, K.C.M. Verhoeckx, S. Bijlsma, C.M. Rubingh, J. Meijerink, H.M. Wortelboer, R.F. Witkamp

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

Abstract

It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we systematically explored the combined effects of n-3 fatty acid diets and inflammation on the in vivo endocannabinoid and oxylipin metabolomes using a multicompartment, detailed targeted lipidomics approach. Male C57BL/6 mice received diets containing 0, 1, or 3 % w/w fish oil (FO) for 6 weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6 fatty acid derived compounds, were determined in plasma, liver, ileum and adipose tissue using LC–MS/MS. FO generally increased ‘n-3’ NAEs and oxylipins at the expense of compounds derived from other fatty acids, affecting all branches of the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs and oxylipins, with opposing effects across plasma and tissues. Multivariate data analysis revealed that separation between diet groups in the saline treated groups was primarily explained by decreases in other than n-3 derived compounds. In the LPS treated groups, the separation was primarily explained by increases in n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes, with specific effects depending on inflammatory status.
Original languageEnglish
Pages (from-to)1130-1147
JournalMetabolomics
Volume8
Issue number6
DOIs
Publication statusPublished - 2012

Fingerprint

Oxylipins
Endocannabinoids
Metabolome
Fish Oils
Tissue
Plasmas
Nutrition
Omega-3 Fatty Acids
Diet
Fatty Acids
Inflammation
Inbred C57BL Mouse
Ileum
Liver
Adipose Tissue
Anti-Inflammatory Agents
Multivariate Analysis
Modulation

Keywords

  • polyunsaturated fatty-acids
  • n-acylethanolamines
  • eicosapentaenoic acid
  • lipid mediators
  • endogenous cannabinoids
  • docosahexaenoic acid
  • amide hydrolase
  • anandamide
  • liver
  • docosatrienes

Cite this

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title = "Fish oil and inflammatory status alter the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes in mouse plasma and tissues",
abstract = "It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we systematically explored the combined effects of n-3 fatty acid diets and inflammation on the in vivo endocannabinoid and oxylipin metabolomes using a multicompartment, detailed targeted lipidomics approach. Male C57BL/6 mice received diets containing 0, 1, or 3 {\%} w/w fish oil (FO) for 6 weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6 fatty acid derived compounds, were determined in plasma, liver, ileum and adipose tissue using LC–MS/MS. FO generally increased ‘n-3’ NAEs and oxylipins at the expense of compounds derived from other fatty acids, affecting all branches of the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs and oxylipins, with opposing effects across plasma and tissues. Multivariate data analysis revealed that separation between diet groups in the saline treated groups was primarily explained by decreases in other than n-3 derived compounds. In the LPS treated groups, the separation was primarily explained by increases in n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes, with specific effects depending on inflammatory status.",
keywords = "polyunsaturated fatty-acids, n-acylethanolamines, eicosapentaenoic acid, lipid mediators, endogenous cannabinoids, docosahexaenoic acid, amide hydrolase, anandamide, liver, docosatrienes",
author = "M.G.J. Balvers and K.C.M. Verhoeckx and S. Bijlsma and C.M. Rubingh and J. Meijerink and H.M. Wortelboer and R.F. Witkamp",
year = "2012",
doi = "10.1007/s11306-012-0421-9",
language = "English",
volume = "8",
pages = "1130--1147",
journal = "Metabolomics",
issn = "1573-3882",
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Fish oil and inflammatory status alter the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes in mouse plasma and tissues. / Balvers, M.G.J.; Verhoeckx, K.C.M.; Bijlsma, S.; Rubingh, C.M.; Meijerink, J.; Wortelboer, H.M.; Witkamp, R.F.

In: Metabolomics, Vol. 8, No. 6, 2012, p. 1130-1147.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Fish oil and inflammatory status alter the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes in mouse plasma and tissues

AU - Balvers, M.G.J.

AU - Verhoeckx, K.C.M.

AU - Bijlsma, S.

AU - Rubingh, C.M.

AU - Meijerink, J.

AU - Wortelboer, H.M.

AU - Witkamp, R.F.

PY - 2012

Y1 - 2012

N2 - It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we systematically explored the combined effects of n-3 fatty acid diets and inflammation on the in vivo endocannabinoid and oxylipin metabolomes using a multicompartment, detailed targeted lipidomics approach. Male C57BL/6 mice received diets containing 0, 1, or 3 % w/w fish oil (FO) for 6 weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6 fatty acid derived compounds, were determined in plasma, liver, ileum and adipose tissue using LC–MS/MS. FO generally increased ‘n-3’ NAEs and oxylipins at the expense of compounds derived from other fatty acids, affecting all branches of the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs and oxylipins, with opposing effects across plasma and tissues. Multivariate data analysis revealed that separation between diet groups in the saline treated groups was primarily explained by decreases in other than n-3 derived compounds. In the LPS treated groups, the separation was primarily explained by increases in n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes, with specific effects depending on inflammatory status.

AB - It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we systematically explored the combined effects of n-3 fatty acid diets and inflammation on the in vivo endocannabinoid and oxylipin metabolomes using a multicompartment, detailed targeted lipidomics approach. Male C57BL/6 mice received diets containing 0, 1, or 3 % w/w fish oil (FO) for 6 weeks, after which 2 mg/kg LPS or saline was administered i.p. Levels of endocannabinoids/N-acylethanolamines (NAEs) and oxylipins, covering n-3 and n-6 fatty acid derived compounds, were determined in plasma, liver, ileum and adipose tissue using LC–MS/MS. FO generally increased ‘n-3’ NAEs and oxylipins at the expense of compounds derived from other fatty acids, affecting all branches of the oxylipin metabolome. LPS generally increased levels of endocannabinoids/NAEs and oxylipins, with opposing effects across plasma and tissues. Multivariate data analysis revealed that separation between diet groups in the saline treated groups was primarily explained by decreases in other than n-3 derived compounds. In the LPS treated groups, the separation was primarily explained by increases in n-3 derived compounds. In conclusion, FO caused marked changes in the n-3 to n-6 balance of the endocannabinoid and oxylipin metabolomes, with specific effects depending on inflammatory status.

KW - polyunsaturated fatty-acids

KW - n-acylethanolamines

KW - eicosapentaenoic acid

KW - lipid mediators

KW - endogenous cannabinoids

KW - docosahexaenoic acid

KW - amide hydrolase

KW - anandamide

KW - liver

KW - docosatrienes

U2 - 10.1007/s11306-012-0421-9

DO - 10.1007/s11306-012-0421-9

M3 - Article

VL - 8

SP - 1130

EP - 1147

JO - Metabolomics

JF - Metabolomics

SN - 1573-3882

IS - 6

ER -