Enkephalinase activity is modified and correlates with fatty acids in frontal cortex depending on fish, olive or coconut oil used in the diet

Open access


Objective. Enkephalins are neuropeptides involved in functions such as pain modulation and/ or cognitive processes. It has been reported that dietary fat modifies enkephalins in the brain. Since enkephalins are hydrolyzed by enkephalinases, the study of the influence of dietary fats, differing in their degree of saturation, on brain fatty acids content and enkephalinase activity is important to understand its regulatory role on neuropeptides under different type of diets.

Methods. We analyzed enkephalinase activity, assayed with alanine-β-naphthylamide as sub-strate, in frontal cortex of adult male rats fed diets supplemented with fish oil, olive oil or coconut oil, which markedly differed in the saturation of their fatty acids.

Results. Rats fed a diet enriched with coconut oil had lower soluble enkephalinase activity than the group fed olive oil (p<0.01) and fish oil (p<0.05) whereas rats fed a diet enriched with fish oil had lower membrane-bound enkephalinase activity than the group fed with olive (p<0.001) or coconut oil (p<0.05). Significant negative correlations were observed between certain fatty acids and enkephalinase activities in the groups fed with olive and coconut oils. No correlations were observed in the group fed with fish oil.

Conclusions. Dietary fat modifies enkephalinase activity in the frontal cortex depending on the degree of saturation of the used oil. It is postulated that the functions, in which enkephalins are involved, such as pain modulation or cognitive functions, may also be affected according to the type of oil used in the diet.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Banegas I Prieto I Segarra AB Vives F de Gasparo M Duran R de Dios Luna J Ramirez-Sanchez M. Bilateral distribution of enkephalinase activity in the medial prefrontal cortex differs between WKY and SHR rats unilaterally lesioned with 6-hydroxydopamine. Prog Neuropsychopharmacol Biol Psychiatry 75 213–218 2017.

  • Bodnar RJ. Endogenous Opiates and Behavior: 2016. Peptides 101 167–212. 2018.

  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72 248–254 1976.

  • Chang GQ Karatayev O Ahsan R Gaysinskaya V Marwil Z Leibowitz SF. Dietary fat stimulates endogenous enkephalin and dynorphin in the paraventricular nucleus: role of circulating triglycerides. Am J Physiol Endocrinol Metab 292 E561–E570 2007.

  • Chang GQ Karatayev O Barson JR Chang SY Leibowitz SF. Increased encephalin in brain of rats prone to overconsuming a fat-rich diet. Physiol Behav 101 360–369 2010.

  • Corder G Castro DC Bruchas MR Scherrer G. Endogenous and exogenous opioids in pain. Annu Rev Neurosci 41 453–473 2018.

  • Danziger RS. Aminopeptidase N in arterial hypertension. Heart Fail Rev 13 293–298 2007.

  • de Gandarias JM Casis L Irazusta J Echevarria E Ramirez M. Changes of aminopeptidase activity levels in serum and brain during the estrous cycle of the rat. Horm Metab Res 20 776 1988.

  • de Gandarias JM Ramirez M Zulaica J Casis L. Aminopeptidase (arylamidase) activity in discrete areas of the rat brain: sex differences. Horm Metab Res 21 285–286 1989.

  • Dominguez-Vias G Aretxaga-Maza G Prieto I Segarra AB Luna JD de Gasparo M Ramirez-Sanchez M. Light-dark influence of enkephalinase activity in hypothalamus and pituitary. Neuro Endocrinol Lett 39 277–280 2018.

  • Folch J Less M Sloane-Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226 497–509 1957.

  • Gibson AM Biggins JA Lauffart B Mantle D McDermott JR. Human brain leucyl aminopeptidase: isolation characterization and specificity against some neuropeptides. Neuropeptides 19 163–168 1991.

  • Hardy SG Haigler HJ. Prefrontal influences upon the midbrain: a possible route for pain modulation. Brain Res 339 285–293 1985.

  • Hashimoto M Hossain S Al Mamun A Matsuzaki K Arai H. Docosahexaenoic acid: one molecule diverse functions. Crit Rev Biotechnol 37 579–597 2017.

  • Henry MS Gendron L Tremblay ME Drolet G. Enkephalins: Endogenous analgesics with an emerging role in stress resilience. Neural Plast 2017 1546125 2017.

  • Hernandez J Prieto I Segarra AB de Gasparo M Wangensteen R Villarejo AB Banegas I Vives F Cobo J Ramirez-Sanchez M. Interaction of neuropeptidase activities in cortico-limbic regions after acute restraint stress. Behav Brain Res 287 42–48 2015.

  • Hersh LB. Characterization of membrane-bound aminopeptidases from rat brain: identification of the enkephalin-degrading aminopeptidase. J Neurochem 44 1427–1435 1985.

  • Hersh LB Aboukhair N Watson S. Immunohistochemical localization of aminopeptidase M in rat brain and periphery: relationship of enzyme localization and enkephalin metabolism. Peptides 8 523–532 1987.

  • Iuliano L Pacelli A Ciacciarelli M Zerbinati C Fagioli S Piras F Orfei MD Bossu P Pazzelli F Serviddio G Caltagirone C Spalletta G. Plasma fatty acid lipidomics in amnestic mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 36 545–553 2013.

  • Lepage G Roy CG. Direct transesterification of all classes of lipids in a one step reaction. J Lipid Res 27 114–120 1986.

  • Matsumoto H Nagasaka T Hattori A Rogi T Tsuruoka N Mizutani S Tsujimoto M. Expression of placental leucine aminopeptidase/oxytocinase in neuronal cells and its action on neuronal peptides. Eur J Biochem 268 3259–3266 2001.

  • Mendez IA Ostlund SB Maidment NT Murphy NP. Involvement of endogenous enkephalins and β-endorphin in feeding and diet-induced obesity. Neuropsychopharmacology 40 2103–2112 2015.

  • Moon ML Joesting JJ Lawson MA Chiu GS Blevins NA Kwakwa KA Freund GG. The saturated fatty acid palmitic acid induces anxiety-like behavior in mice. Metabolism 63 1131–1140 2014.

  • Narita M Kaneko C Miyoshi K Nagumo Y Kuzumaki N Nakajima M Nanjo K Matsuzawa K Yamazaki M Suzuki T. Chronic pain induces anxiety with concomitant changes in opioidergic function in the amygdala. Neuropsychopharmacology 31 739–750 2006.

  • Nasaruddin ML Pan X McGuinness B Passmore P Kehoe PG Holscher C Graham SF Green BD. Evidence that parietal lobe fatty acids may be more profoundly affected in moderate Alzheimer’s disease (AD) pathology than in severe AD pathology. Metabolites 8 pii: E69 2018.

  • Paxinos G Watson C. The Rat brain in stereotaxic coordinates. 4th ed. London: Academic Press 1998.

  • Ramirez M Prieto I Banegas I Segarra AB Alba F. Neuropeptidases. Methods Mol Biol 789 287–294 2011.

  • Ruiz-Sanz JI Navarro R Martinez R Martin C Lacort M Matorras R Ruiz-Larrea MB. 17beta-estradiol affects in vivo the low density lipoprotein composition particle size and oxidizability. Free Radic Biol Med 31 391–397 2001.

  • Schommer J Marwarha G Nagamoto-Combs K Ghribi O. Palmitic acid-enriched diet increases α-sSynuclein and tyrosine hydroxylase expression levels in the mouse brain. Front Neurosci 12 552 2018.

  • Segarra AB Ramirez M Banegas I Alba F Vives F de Gasparo M Ortega E Ruiz E Prieto I. Dietary fat influences testosterone cholesterol aminopeptidase A and blood pressure in male rats. Horm Metab Res 40 289–291 2008.

  • Segarra AB Ruiz-Sanz JI Ruiz-Larrea MB Ramirez-Sanchez M de Gasparo M Banegas I Martinez-Canamero M Vives F Prieto I. The profile of fatty acids in frontal cortex of rats depends on the type of fat used in the diet and correlates with neuropeptidase activities. Horm Metab Res 43 86–91 2011.

  • Thompson MW Hersh LB. The puromycinsensitive aminopeptidase; in Hooper NM Lendeckel U (eds): Aminopeptidases in Biology and Disease. Kluwer Academic/Plenum New York 2004 pp 1–15.

Journal information
Impact Factor

CiteScore 2018: 1.27

SCImago Journal Rank (SJR) 2018: 0.411
Source Normalized Impact per Paper (SNIP) 2018: 0.441

Cited By
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 252 252 24
PDF Downloads 187 187 20