#cparse("/super/config/super.config.vm") #cparse ("/includes/site.config.fhtml") #cparse("${directoryRoot}/config/2col.config.vm") ## siteSection - tab to highlight on top navigation #set ($siteSection = "lipidomics update") #set ($siteSubSection = "archives") ## Webtrends #set($WT_cg_n = "Lipidomics Update") #set($WT_cg_s = "Articles") #cparse("${superIncludes}/super.before-doctype.fhtml") #cparse("${directoryIncludes}/doctype.fhtml") #cparse("${superIncludes}/super.head-top.fhtml") N-oleoyl ethanolamine (OEA) : $siteName #set($metaDescription = "How not to over-eat: stop eating when full and do not eat again too soon. OEA, released in response to dietary fat intake, prolongs the interval between meals and facilitates uptake of fat. This multi-talented lipid mediator is also implicated in neuroprotection, memory consolidation and stress response.") #cparse("${directoryIncludes}/metalink.fhtml") #cparse("${directoryIncludes}/style.fhtml") #cparse("${superIncludes}/super.head-bottom.fhtml") #cparse("${superIncludes}/super.body-top.fhtml") #cparse("${directoryIncludes}/header.fhtml") #cparse("${common}/includes/clearfloats.fhtml")

N-oleoyl ethanolamine (OEA)

Lipidomics Gateway (27 May 2009) [doi:10.1038/lipidmaps.2009.9]

How not to over-eat: stop eating when full and do not eat again too soon. OEA, released in response to dietary fat intake, prolongs the interval between meals and facilitates uptake of fat. This multi-talented lipid mediator is also implicated in neuroprotection, memory consolidation and stress response.

Space-filling model of N-oleoyl ethanolamine. Visit N-oleoyl ethanolamine in the LIPID MAPS database for more molecular information.

N-oleoyl ethanolamine (OEA, also known as oleoylethanolamide) is related to the endocannabinoid anandamide. Endocannabinoids signal through cannabinoid receptors (also stimulated by the active ingredient of cannabis) but although related in structure, synthesis and degradation to anandamide, OEA cannot be considered an endocannabinoid as it does not activate the cannabinoid receptors. Most of the reported responses to OEA can be attributed to activation of peroxisome proliferator-activated receptor-α (PPAR-α) 1 2 3 .

From fast to fat: handling ingestion of a fatty meal

OEA activation of PPAR-α stimulates the expression of enzymes involved in lipid transport and metabolism. Oleic acid, a major digestive product of dietary fat, is transported into small-intestinal enterocytes by the fatty acid translocase CD36, from where a fraction is converted to OEA. This acts as a sensor for ingestion of fat, activating PPAR-α to enhance lipid absorption (including by increased expression of CD36) 4 . Giving the body time to handle the metabolic challenge presented by a fatty meal, OEA affects sensory vagus nerve activity through PPAR-α to induce satiety and decrease meal frequency. It does not impact upon the size of a meal: satiation prompts meal termination and is mediated by gut peptides, whereas satiety is a separate response. The exact mechanism linking PPAR-α with the neural and behavioral response is not known.

Staying slim: OEA inhibits weight gain

Administration of OEA inhibits body weight gain in rats. In adipocytes and hepatocytes, OEA inhibits mitogenic and metabolic signaling by the insulin receptor and produces glucose intolerance 5 . It also inhibits gastric emptying, which might act together with the sensory neuronal signals to achieve satiety. Permanently elevated in diabetic obese patients, levels of OEA are potential therapeutic targets for treatment of obesity, diabetes and eating disorders 1 .

Whole body effects: appetite, sleep, stress and memory

One of our June Research highlights, Remembering dinner: OEAsy does it, describes a novel connection between OEA, PPAR-α and the consolidation of recent memories 6 . This is not the only 'extracurricular' OEA response: other effects hint at the complex relationship between appetite, stress and sleep. In human volunteers, OEA levels were raised in cerebrospinal fluid (but not serum) after 24 hours of sleep deprivation, postulated as a neuroprotective response 7 . Thirty minutes after a social stress test OEA levels were decreased in human serum 8 . In mice, OEA blocked stress-induced acceleration of upper gastrointestinal transit at a dose too low to inhibit normal transit 9 . Treatment of diarrhea-predominant irritable bowel syndrome, or even of stress in general, can therefore be added to the potential exploitation of this powerful lipid mediator.

Emma Leah

- Copyright © 2009 Nature Publishing Group, a division of Macmillan Publishers Limited; used with permission

References:

  1. Capasso, R. & Izzi, A. A. Gastrointestinal regulation of food intake: general aspects and focus on anandamide and oleoylethanolamide.

    J. Neuroendocrinol. 20, 39-46 (2008). doi:10.1111/j.1365-2826.2008.01686.x

  2. Hansen, H. S. & Artmann, A. Endocannabinoids and Nutrition.

    J. Neuroendocrinol. 20, 94-99 (2008). doi:10.1111/j.1365-2826.2008.01687.x

  3. Brown, A. J. Novel cannabinoid receptors.

    British Journal of Pharmacology 152, 567-575 (2007). doi:10.1038/sj.bjp.0707481

  4. Schwartz, G. J. et al. The lipid messenger OEA links dietary fat intake to satiety.

    Cell Metabolism 8, 281-288 (2008). doi:10.1016/j.cmet.2008.08.005

  5. de Ubago, M. M. et al. Oleoylethanolamide, a natural ligand for PPAR-alpha, inhibits insulin receptor signalling in HTC rat hepatoma cells.

    Biochim Biophys Acta. (Apr 5 2009). doi:10.1016/j.bbalip.2009.03.014

  6. Campolongo, P. et al. Fat-induced satiety factor oleoylethanolamide enhances memory consolidation.

    Proc. Nat. Acad. Sci. USA 106, 8027-8031 (2009). doi:10.1073/pnas.0903038106

  7. Koethe, D. et al. Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid.

    J. Neural Transm. 116, 301-305 (2009). doi:10.1007/s00702-008-0169-6

  8. Hill, M. N. et al. Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress.

    Psychoneuroendocrinology (Apr 24 2009). doi:10.1016/j.psyneuen.2009.03.013

  9. Cluny, N. L. et al. The identification of peroxisome proliferator-activated receptor alpha-independent effects of oleoylethanolamide on intestinal transit in mice.

    Neurogastroenterol Motil 21, 420-429 (2009). doi:10.1111/j.1365-2982.2008.01248.x

#cparse("${directoryIncludes}/search.fhtml") #cparse("${directoryIncludes}/links.fhtml") #cparse("${directoryIncludes}/resources.fhtml")
#cparse("${common}/includes/clearfloats.fhtml") #cparse("${directoryIncludes}/footer.fhtml") #cparse("${superIncludes}/super.body-bottom.fhtml")