Vaccenic acid suppresses intestinal inflammation by increasing anandamide and related N-acylethanolamines in the JCR:LA-cp rat[S]

• Published in: Journal of lipid research 2016-04, Vol.57 (4), p.638-649
• Main Authors: Jacome-Sosa, Miriam, Vacca, Claudia, Mangat, Rabban, Diane, Abdoulaye, Nelson, Randy C., Reaney, Martin J., Shen, Jianheng, Curtis, Jonathan M., Vine, Donna F., Field, Catherine J., Igarashi, Miki, Piomelli, Daniele, Banni, Sebastiano, Proctor, Spencer D.
• Format: Article
• Language: English
• Subjects: Amidohydrolases - genetics; Amidohydrolases - metabolism; anandamide; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Arachidonic Acids - metabolism; Caco-2 Cells; Cytokines - genetics; Cytokines - metabolism; Dietary Supplements; Disease Models, Animal; endocannabinoids; Endocannabinoids - metabolism; Ethanolamines - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Humans; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; intestinal inflammatory diseases; Intestinal Mucosa - metabolism; Intestines - drug effects; Intestines - pathology; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - metabolism; Liver - drug effects; Liver - metabolism; Male; Membrane Lipids - metabolism; Metabolic Syndrome - metabolism; N-acylethanolamines; Oleic Acids - pharmacology; Oleic Acids - therapeutic use; Polyunsaturated Alkamides - metabolism; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; vaccenic acid
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M066308

Vaccenic acid (VA), the predominant ruminant-derived trans fat in the food chain, ameliorates hyperlipidemia, yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (ECs) by altering the availability of their biosynthetic precursor, arachidonic acid (AA), in membrane phospholipids (PLs). JCR:LA-cp rats were assigned to a control diet with or without VA (1% w/w), cis-9, trans-11 conjugated linoleic acid (CLA) (1% w/w) or VA+CLA (1% + 0.5% w/w) for 8 weeks. VA reduced the EC, 2-arachidonoylglycerol (2-AG), in the liver and visceral adipose tissue (VAT) relative to control diet (P < 0.001), but did not change AA in tissue PLs. There was no additive effect of combining VA+CLA on 2-AG relative to VA alone (P > 0.05). Interestingly, VA increased jejunal concentrations of anandamide and those of the noncannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to control diet (P < 0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase, as well as the mRNA expression of TNFα and interleukin 1β (P < 0.05). The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of ECs and other noncannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine.