Relative abundance of short chain and polyunsaturated fatty acids in propionic acid-induced autistic features in rat pups as potential markers in autism
Open accessAbstract
BACKGROUND: Fatty acids are essential dietary nutrients, and one of their important roles is providing polyunsaturated fatty acids (PUFAs) for the growth and function of nervous tissue. Short chain fatty acids (SCFAs) are a group of compounds derived from the host microbiome that were recently linked to effects on the gut, the brain, and behavior. They are therefore linked to neurodevelopmental disorders such as autism. Reduced levels of PUFAs are associated with impairments in cognitive and behavioral performance, which are particularly important during brain development. Recent studies suggest that omega -3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are involved in neurogenesis, neurotransmission, and protection from oxidative stress. Omega-3 PUFAs mediate some of these effects by antagonizing Omega-6 PUFA (arachidonic acid, AA)-induced proinflammatory prostaglandin E₂ (PGE₂) formation. METHODS: In this work, the absolute and relative concentrations of propionic (PPA), butyric and acetic acids, as well as PUFAs and their precursors (α-Linolenic and linoleic), were measured in the brain tissue of PPA-neurointoxicated rat pups (receiving 250 mg PPA/Kg body weight for 3 consecutive days) as a rodent model with persistent autistic features compared with healthy controls. RESULTS: The data revealed remarkably lower levels of omega6/omega3, α-Linolenic/Linoleic, α-Linolenic/EPA, α-Linolenic/DHA, EPA/DHA, and AA/Linoleic acid ratios in PPA-intoxicated rats. The role of these impaired ratios is discussed in relation to the activity of desaturases and elongases, which are the two enzymatic groups involved in the synthesis of PUFAs from their precursors. The relationship between the abnormal relative concentrations of the studied fatty acids and oxidative stress, neurotransmission, and neuroinflammation is also discussed in detail. CONCLUSIONS: This study demonstrates that fatty acid ratios are useful for understanding the mechanism of PPA neurotoxicity in a rodent model of autism. Therefore, it is possible to use these ratios for predictions in patients with this disorder.
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Propionate modulates 5-HT secretion in the gut and depletes 5-HT and dopamine levels in the brain, which could contribute to hyperserotonemia observed in children with ASD.
“In addition to direct effects on the brain, propionate has been shown to modulate 5-hydroxytryptamine (5’-HT) secretion in the gut and deplete 5’-HT and dopamine levels in the brain, which could potentially contribute to the hyperserotonemia observed in children with ASD [182,183,184].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [183]
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A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
The Fluid Mosaic Model of the Structure of Cell Membranes
Singer, S. J., & Nicolson, G. L. (1972) · Science · doi:10.1126/science.175.4023.720 · Cited by 9,158 · see citing works
The Statistical Evaluation of Medical Tests for Classification and Prediction
PEPE, M. S. (2003) · doi:10.1093/oso/9780198509844.001.0001 · Cited by 2,206 · see citing works
The Statistical Evaluation of Medical Tests for Classification and Prediction
PEPE, M. S. (2005) · Technometrics · doi:10.1198/tech.2005.s278 · Cited by 1,907 · see citing works
Regulation of inflammation by short chain fatty acids
Vinolo, M. A. R., Rodrigues, H. G., Nachbar, R. T., & Curi, R. (2011) · Nutrients · doi:10.3390/nu3100858 · Cited by 1,724 · see citing works
MOLECULAR BASIS FOR MEMBRANE PHOSPHOLIPID DIVERSITY: Why Are There So Many Lipids?
Dowhan, W. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.199 · Cited by 1,007 · see citing works
Vinolo, M. A. R., Rodrigues, H. G., Hatanaka, E., Sato, F. T., Sampaio, S. C., & Curi, R. (2010) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.07.009 · Cited by 714 · see citing works
Essential Fatty Acids: Biochemistry, Physiology and Pathology
Das, U. N. (2006) · Biotechnology Journal · doi:10.1002/biot.200600012 · Cited by 650 · see citing works
The Biology of Mitochondrial Uncoupling Proteins
Rousset, S., Alves‐Guerra, M., Mozo, J., Miroux, B., Cassard, A., Bouillaud, F., & Ricquier, D. (2004) · Diabetes · doi:10.2337/diabetes.53.2007.s130 · Cited by 556 · see citing works
MACFABE, D., CAIN, D., RODRIGUEZCAPOTE, K., FRANKLIN, A., HOFFMAN, J., BOON, F., TAYLOR, A., KAVALIERS, M., & OSSENKOPP, K. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.07.025 · Cited by 497 · see citing works
Säemann, M. D., Böhmig, G. A., Österreicher, C. H., BURTSCHER, H. J., Parolini, O., Diakos, C., Stöckl, J., Hörl, W. H., & Zlabinger, G. J. (2000) · The FASEB Journal · doi:10.1096/fj.00-0359fje · Cited by 482 · see citing works
Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival
Akbar, M. D., Calderón, F. H., Wen, Z., & Kim, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502903102 · Cited by 466 · see citing works
Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder
Stevens, L., Zentall, S., Deck, J., Abate, M., Watkins, B. A., Lipp, S., & Burgess, J. R. (1995) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/62.4.761 · Cited by 445 · see citing works
Chen, W.-J. L., Anderson, J. W., & Jennings, D. (1984) · Experimental Biology and Medicine · doi:10.3181/00379727-175-41791 · Cited by 439 · see citing works
Bazan, N. G. (2006) · Brain Pathology · doi:10.1111/j.1750-3639.2005.tb00513.x · Cited by 367 · see citing works
Gamma Linolenic Acid: An Antiinflammatory Omega-6 Fatty Acid
Kapoor, R. K., & Huang, Y. S. (2006) · Current Pharmaceutical Biotechnology · doi:10.2174/138920106779116874 · Cited by 356 · see citing works
Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3
Darios, F. D., & Davletov, B. A. (2006) · Nature · doi:10.1038/nature04598 · Cited by 352 · see citing works
Xiao, Y., Kang, J. X., Morgan, J. P., & Leaf, A. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.24.11000 · Cited by 332 · see citing works
Weatherill, A. R., Lee, J. Y., Zhao, L., Lemay, D. G., Youn, H. S., & Hwang, D. H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.9.5390 · Cited by 312 · see citing works
Polyunsaturated fatty acids modulate sodium and calcium currents in CA1 neurons.
Vreugdenhil, M., Bruehl, C., Voskuyl, R. A., Kang, J. X., Leaf, A., & Wadman, W. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.22.12559 · Cited by 304 · see citing works
Park, J.-S., Lee, E.-J., Lee, J.-C., Kim, W.-K., & Kim, H.-S. (2007) · International Immunopharmacology · doi:10.1016/j.intimp.2006.08.015 · Cited by 278 · see citing works
Novel Anti-Inflammatory-Pro-Resolving Mediators and Their Receptors
Serhan, C. N., Krishnamoorthy, S., Recchiuti, A., & Chiang, N. (2011) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026611109060629 · Cited by 278 · see citing works
Regulation of microglial inflammatory response by sodium butyrate and short‐chain fatty acids
Huuskonen, J., Suuronen, T., Nuutinen, T., Kyrylenko, S., & Salminen, A. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705682 · Cited by 274 · see citing works
Liu, T., Li, J., Liu, Y., Xiao, N., Suo, H., Xie, K., Yang, C., & Wu, C. (2012) · Inflammation · doi:10.1007/s10753-012-9484-z · Cited by 248 · see citing works
Mullen, A., Loscher, C. E., & Roche, H. M. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2009.02.008 · Cited by 240 · see citing works
Regulated formation of eicosanoids
Fitzpatrick, F. A., & Soberman, R. J. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13241 · Cited by 232 · see citing works
Felder, C. C., Kanterman, R. Y., Ma, A. L., & Axelrod, J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.6.2187 · Cited by 220 · see citing works
Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children
Al-Gadani, Y., El-Ansary, A. K., Al-Attas, O., & AL-Ayadhi, L. Y. (2009) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2009.03.011 · Cited by 216 · see citing works
Self-citationEtiology of autistic features: the persisting neurotoxic effects of propionic acid
El-Ansary, A. K., Bacha, A. B., & Kotb, M. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-74 · Cited by 209 · see citing works
Wajner, M., Latini, A., Wyse, Â. T. D. S., & Dutra‐Filho, C. S. (2004) · Journal of Inherited Metabolic Disease · doi:10.1023/b:boli.0000037353.13085.e2 · Cited by 191 · see citing works
Long-chain polyunsaturated fatty acids in the growth and development of the brain and memory
Das, U. N. (2002) · Nutrition · doi:10.1016/s0899-9007(02)00852-3 · Cited by 177 · see citing works
Anderson, J. W., & Bridges, S. R. (1984) · Experimental Biology and Medicine · doi:10.3181/00379727-177-41958 · Cited by 163 · see citing works
Arachidonic Acid and the Brain
Rapoport, S. I. (2008) · Journal of Nutrition · doi:10.1093/jn/138.12.2515 · Cited by 157 · see citing works
Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-κB
Venkatraman, A., Ramakrishna, B., Velayudhan, S. R., Kumar, N. S. N., Pulimood, A. B., & Patra, S. (2003) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00307.2002 · Cited by 138 · see citing works
Association of Fatty Acid Desaturase Genes with Attention-Deficit/Hyperactivity Disorder
Brookes, K. J., Chen, W., Xu, X., Taylor, E. A., & Asherson, P. J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.025 · Cited by 135 · see citing works
Kong, W., Yen, J.-H. J., Vassiliou, E. K., Adhikary, S., Toscano, M. G., & Ganea, D. (2010) · Lipids in Health and Disease · doi:10.1186/1476-511x-9-12 · Cited by 132 · see citing works
Foley, K., Ossenkopp, K., Kavaliers, M., & Macfabe, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087072 · Cited by 128 · see citing works
Arachidonic acid stimulates glucose uptake in cerebral cortical astrocytes.
Yu, N., Martin, J., Stella, N., & Magistretti, P. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4042 · Cited by 120 · see citing works
Thomas, R., Foley, K. A., Mepham, J. R., Tichenoff, L. J., Possmayer, F., & MacFabe, D. F. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06614.x · Cited by 117 · see citing works
Dietary Fibre — A Component of Food
Schweizer, T. F., & Edwards, C. A. (1992) · ILSI human nutrition reviews · doi:10.1007/978-1-4471-1928-9 · Cited by 116 · see citing works
Uncoupling proteins, dietary fat and the metabolic syndrome
Fisler, J. S., & Warden, C. H. (2006) · Nutrition & Metabolism · doi:10.1186/1743-7075-3-38 · Cited by 106 · see citing works
The contribution of the large intestine to blood acetate in man
Scheppach, W. M., Pomare, E. W., Elia, M., & Cummings, J. H. (1991) · Clinical Science · doi:10.1042/cs0800177 · Cited by 106 · see citing works
Garcia, M. C., & Kim, H. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00583-0 · Cited by 101 · see citing works
Assisi, A., Banzi, R., Buonocore, C., Capasso, F., Muzio, V., Michelacci, F., Renzo, D., Tafuri, G., Trotta, F., Vitocolonna, M., et al. (2006) · International Clinical Psychopharmacology · doi:10.1097/01.yic.0000224790.98534.11 · Cited by 101 · see citing works
Excitotoxicity in the Pathogenesis of Autism
Essa, M. M., Braidy, N., Vijayan, K. R., Subash, S., & Guillemin, G. J. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9354-3 · Cited by 97 · see citing works
Molecular Basis of Health and Disease
Das, U. N. (2011) · Springer eBooks · doi:10.1007/978-94-007-0495-4 · Cited by 94 · see citing works
Kuperstein, F., Eilam, R., & Yavin, E. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05418.x · Cited by 81 · see citing works
El-Ansary, A. K., Bacha, A. G. B., & Ayahdi, L. Y. A. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-63 · Cited by 79 · see citing works
Self-citationJones, C. R., Arai, T., Bell, J. M., & Rapoport, S. I. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67020822.x · Cited by 66 · see citing works
Brass, E. P., Fennessey, P. V., & Miller, L. V. (1986) · Biochemical Journal · doi:10.1042/bj2360131 · Cited by 63 · see citing works
Das, U. N. (2002) · Springer eBooks · doi:10.1007/978-1-4419-8564-4 · Cited by 62 · see citing works
Pettenuzzo, L. F. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00856-0 · Cited by 62 · see citing works
Aïd, S., Vancassel, S., Linard, A., Lavialle, M., & Guesnet, P. (2005) · Journal of Nutrition · doi:10.1093/jn/135.5.1008 · Cited by 62 · see citing works
Hajjar, T., Meng, G. Y., Rajion, M. A., et al. (2012) · BMC Neuroscience · doi:10.1186/1471-2202-13-109 · Cited by 59 · see citing works
DeGeorge, J. J., Ousley, A. H., McCarthy, K. D., et al. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47530-8 · Cited by 54 · see citing works
Interactions of n-3 fatty acids with ion channels in excitable tissues
Leaf, A., Xiao, Y., & Kang, J. X. (2002) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1054/plef.2002.0407 · Cited by 47 · see citing works
Potent block of inactivation-deficient Na+channels by n-3 polyunsaturated fatty acids
Xiao, Y., Ma, L., Wang, S., Josephson, M. E., Wang, G. K., Morgan, J. P., & Leaf, A. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00296.2005 · Cited by 44 · see citing works
Metabolic Syndrome Pathophysiology
Das, U. N. (2010) · Wiley eBooks · doi:10.1002/9780813820637 · Cited by 44 · see citing works
Basselin, M., Ramadan, E., & Rapoport, S. I. (2011) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.12.001 · Cited by 43 · see citing works
Narendran, R., Frankle, W. G., Mason, N. S., Muldoon, M. F., & Moghaddam, B. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046832 · Cited by 35 · see citing works
Chisaguano, A. M., Montes, R., Pérez, T., Castellote, A. I., Guerendiain, M., Bustamante, M., Morales, E., García‐Esteban, R., Sunyer, J., Franch, À., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078245 · Cited by 31 · see citing works
Metabolism and Utilisation of Short Chain Fatty Acids Produced by Colonic Fermentation
Rémésy, C., Demigné, C., & Morand, C. (1992) · ILSI human nutrition reviews · doi:10.1007/978-1-4471-1928-9_7 · Cited by 27 · see citing works
Butyric Acid Derivative Induces Allospecific T Cell Anergy and Prevents Graft-Versus-Host Disease
Gilbert, K. M., Boger, S., & Fifer, E. K. (2003) · Immunopharmacology and Immunotoxicology · doi:10.1081/iph-120018280 · Cited by 12 · see citing works
Azavache, V., Cuevas, C., & Bosch, V. (1998) · PubMed · Cited by 3 · see citing works
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- [36]Azavache V Cuevas C Bosch V The liver as a source of LC-PUFA for postnatal brain development in the rat Arch Latinoam Nutr 1998 48 216 220 9951533
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Ristori, M. V., Quagliariello, A., Reddel, S., Ianiro, G., Vicari, S., Gasbarrini, A., & Putignani, L. (2019) · Nutrients · doi:10.3390/nu11112812 · Cited by 214 · see citing works
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- Authors
- El-Ansary, A., & Al-Ayadhi, L.
- Affiliations
- King Saud University (SA)
- Corresponding author
- El-Ansary, Afaf
- Venue
- Lipids in Health and Disease
- Published
- 2014-08-31
- Volume
- 13
- Issue
- 1
- Pages
- 140-140
- ISSN
- 1476-511X (ISSN-L)
- PMC
- PMC4176835
- OpenAlex
- W2022117199
- Cited by
- 35
- References
- 64
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Lipids in Health and Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- King Saud University
- Female Center for Scientific and Medical Colleges, King Saud University
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- autism spectrum disorder, short-chain fatty acids, polyunsaturated fatty acids, n-6/n-3 ratio, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, fatty acid ratio, desaturases, elongases, neuroinflammation, oxidative stress, neurotransmission, gut-brain axis, autism biomarkers, neonatal rats
- MeSH terms
- Animals, Autistic Disorder, Brain, Fatty Acids, Unsaturated, Male, Propionates, ROC Curve, Biomarkers, Area Under Curve, Rats
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