Nitrated oleic acid up-regulates PPARγ and attenuates experimental inflammatory bowel disease
Open accessAbstract
Nitric oxide and its metabolites undergo nitration reactions with unsaturated fatty acids during oxidative inflammatory conditions, forming electrophilic nitro-fatty acid derivatives. These endogenous electrophilic mediators activate anti-inflammatory signaling reactions, serving as high-affinity ligands for peroxisome proliferator-activated receptor gamma (PPARgamma). Here we examined the therapeutic effects of 9- or 10-nitro-octadecenoic oleic acid (OA-NO(2)) and native oleic acid (OA) in a mouse model of colitis. OA-NO(2) reduced the disease activity index and completely prevented dextran sulfate sodium-induced colon shortening and the increase in colonic p65 expression. Increased PPARgamma expression was observed in colon samples as well as in cells after OA-NO(2) administration, whereas no effect was seen with OA. This induction of PPARgamma expression was completely abolished by the PPARgamma antagonist GW9662. 5-Aminosalicylic acid, an anti-inflammatory drug routinely used in the management of inflammatory bowel disease, also increased PPARgamma expression but to a lesser extent. Altogether, these findings demonstrate that administration of OA-NO(2) attenuates colonic inflammation and improves clinical symptoms in experimental inflammatory bowel disease. This protection involves activation of colonic PPARgamma.
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NO2-FA signalling pathways are mediated through S-alkylation of nuclear factor κB (resulting in inhibition of macrophage cytokine and iNOS expression) and peroxisome proliferator-activated receptor-γ (PPAR-γ).
“Signalling pathways are mediated through S-alkylation of, for example, nuclear factor k B (resulting in inhibition of macrophage cytokine and iNOS expression) [194] and peroxisome proliferator-activated receptor-g (PPAR-g) [195].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [195]
Through these signaling mechanisms, nitrated lipids mediate a number of physiological effects in animal models including attenuation of inflammatory bowel disease, protection after ischemia/reperfusion, decreases in atherosclerosis, and reversal of obesity-induced pulmonary hypertension.
“Through these signaling mechanisms, nitrated lipids mediate a number of physiological effects in animal models including attenuation of inflammatory bowel disease (113), protection after ischemia/reperfusion (683, 801), decreases in atherosclerosis (800), and reversal of obesity-induced pulmonary hypertension (495).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [113]
Significant metabolic and anti-inflammatory responses are induced by exogenously-administered fatty acid nitroalkenes in murine models after administration of doses giving 5-10 nM plasma concentrations.
“Significant metabolic and anti-inflammatory responses are induced by exogenously-administered fatty acid nitroalkenes in murine models after administration of doses giving 5–10 nM plasma concentrations [43, 44].”
From Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes (2015) · cites this paper as [44]
Fatty acid nitroalkene administration inhibits the onset of chemically induced inflammatory bowel disease.
“Thus, in murine models of metabolic and inflammatory injury, fatty acid nitroalkene administration at nanomolar concentrations prevents restenosis after vessel injury (49), limits weight gain and loss of insulin sensitivity in murine models of metabolic syndrome (14), protects against ischemia-reperfusion injury (17,47,50), reduces plaque formation in a rodent model of atherosclerosis (51), and in”
From Conjugated linoleic acid is a preferential substrate for fatty acid nitration (2012) · cites this paper as [52]
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Cites
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · see citing works
Self-citationRubbo, H., Radí, R., Trujillo, M., Telleri, R., Kalyanaraman, B., Barnes, S., KIRK, M. C., & Freeman, B. Α. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47160-8 · Cited by 1,350 · see citing works
Self-citationA novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response
Su, C. G., Wen, X., Bailey, S. T., Jiang, W. G., Rangwala, S. M., Keilbaugh, S. A., Flanigan, A., Murthy, S., Lazar, M. A., & Wu, G. D. (1999) · Journal of Clinical Investigation · doi:10.1172/jci7145 · Cited by 769 · see citing works
Nitrate, bacteria and human health
Lundberg, J. O., Weitzberg, E., Cole, J. A., & Benjamin, N. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro929 · Cited by 739 · see citing works
Self-citationIntragastric nitric oxide production in humans: measurements in expelled air.
Lundberg, J. O., Weitzberg, E., Lundberg, J. M., & Alving, K. (1994) · Gut · doi:10.1136/gut.35.11.1543 · Cited by 661 · see citing works
Self-citationRousseaux, C., Lefebvre, B., Dubuquoy, L., Lefèbvre, P., Romano, O., Auwerx, J. H., METZGER, D., Wahli, W., Desvergne, B., Naccari, G. C., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041948 · Cited by 528 · see citing works
Desreumaux, P., Dubuquoy, L., Nutten, S., Peuchmaur, M. M., Englaro, W., Schoonjans, K., Dérijard, B., Desvergne, B., Wahli, W., Chambon, P., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.7.827 · Cited by 458 · see citing works
PPARγ as a new therapeutic target in inflammatory bowel diseases
Dubuquoy, L., Rousseaux, C., Thuru, X., Peyrin-Biroulet, L., Romano, O., Chavatte, P., Chamaillard, M., & Desreumaux, P. (2006) · Gut · doi:10.1136/gut.2006.093484 · Cited by 450 · see citing works
Nitrolinoleic acid. An endogenous peroxisome proliferator-activated receptor γ ligand
Schopfer, F. J., Lin, Y., Baker, P. R. S., Cui, T., Garcia-Barrio, M., Zhang, J., Chen, K., Chen, Y. E., & Freeman, B. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408384102 · Cited by 428 · see citing works
Self-citationLichtenstein, G. R., Abreu, M. T., Cohen, R. D., & Tremaine, W. J. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.01.048 · Cited by 424 · see citing works
Bassaganya-Riera, J., Reynolds, K., Martino‐Catt, S. J., Cui, Y., Hennighausen, L. G., Gonzalez, F. J., Rohrer, J., Uribe-Benninghoff, A., & Hontecillas, R. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.06.049 · Cited by 393 · see citing works
Lichtenstein, G. R., Sbreu, M. T., Cohen, R. D., & Tremaine, W. J. (2006) · PubMed · Cited by 370 · see citing works
Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice
Ito, R., Shin‐Ya, M., Kishida, T., Urano, A., Takada, R., Sakagami, J., Imanishi, J., Kita, M., Ueda, Y., Iwakura, Y., et al. (2006) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2006.03214.x · Cited by 365 · see citing works
Fatty Acid Transduction of Nitric Oxide Signaling
Baker, P. R. S., Lin, Y., Schopfer, F. J., Woodcock, S. R., Groeger, A. L., Batthyany, C., Sweeney, S., Long, M. H., Iles, K. E., Baker, L. M. S., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504212200 · Cited by 358 · see citing works
Self-citationNitrated Fatty Acids: Endogenous Anti-inflammatory Signaling Mediators
Cui, T., Schopfer, F. J., Zhang, J., Chen, K., Ichikawa, T., Baker Paul, R. S., Batthyany, C., Chacko, B. K., Feng, X., Patel, R. P., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603357200 · Cited by 351 · see citing works
Self-citationGreatly increased luminal nitric oxide in ulcerative colitis
Lundberg, J. O. N., Lundberg, J. M., Alving, K., & Hellström, P. M. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90460-x · Cited by 266 · see citing works
Self-citationRosiglitazone for Active Ulcerative Colitis: A Randomized Placebo-Controlled Trial
Lewis, J. D., Lichtenstein, G. R., Deren, J. J., Sands, B. E., Hanauer, S. B., Katz, J. A., Lashner, B. A., Present, D. H., Chuai, S., Ellenberg, J. H., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.12.012 · Cited by 229 · see citing works
Adachi, M., Kurotani, R., Morimura, K., Shah, Y. M., Sanford, M., Madison, B. B., Gumucio, D. L., Marin, H. E., Peters, J. M., Young, H. A., et al. (2006) · Gut · doi:10.1136/gut.2005.081745 · Cited by 210 · see citing works
Mediterrranean Diet and Health Biological Importance of Olive Oil
la Lastra, C., Barranco, M., Motilva, V., et al. (2001) · Current Pharmaceutical Design · doi:10.2174/1381612013397654 · Cited by 201 · see citing works
Baker, P. R. S., Schopfer, F. J., Sweeney, S., & Freeman, B. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402587101 · Cited by 201 · see citing works
Self-citationNitro-fatty Acid Reaction with Glutathione and Cysteine
Baker, L. M. S., Baker, P. R. S., Golin-Bisello, F., Schopfer, F. J., Fink, M., Woodcock, S. R., Branchaud, B. P., Radi, R., & Freeman, B. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704085200 · Cited by 200 · see citing works
Self-citationChen, C., Shah, Y., Morimura, K., Krausz, K., Miyazaki, M., Richardson, T. A., Morgan, E. T., Ntambi, J., Idle, J., & Gonzalez, F. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.12.003 · Cited by 183 · see citing works
An open-label trial of the PPARgamma ligand rosiglitazone for active ulcerative colitis
Lewis, J. D., Lichtenstein, G. R., Stein, R. B., Deren, J. J., Judge, T. A., Fogt, F., Furth, E. E., Demissie, E., Hurd, L. B., Su, C. G., et al. (2001) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.05333.x · Cited by 181 · see citing works
Katayama, K., Wada, K., Nakajima, A., Mizuguchi, H., Hayakawa, T., Nakagawa, S., Kadowaki, T., Nagai, R., Kamisaki, Y., Blumberg, R. S., et al. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00262-2 · Cited by 176 · see citing works
Molecular recognition of nitrated fatty acids by PPARγ
Li, Y., Zhang, J., Schopfer, F. J., Martynowski, D., Garcia-Barrio, M. T., Kovach, A., Suino-Powell, K., Baker, P. R. S., Freeman, B. A., Chen, Y. E., et al. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1447 · Cited by 168 · see citing works
Self-citationSaubermann, L. J., Nakajima, A., Wada, K., Zhao, S., Terauchi, Y., Kadowaki, T., Aburatani, H., Matsuhashi, N., Nagai, R., & Blumberg, R. S. (2002) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200209000-00004 · Cited by 164 · see citing works
Diaz-Granados, N., Howe, K. L., Lu, J. G., & McKay, D. M. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65087-0 · Cited by 131 · see citing works
Nitro-fatty Acid Metabolome: Saturation, Desaturation, β-Oxidation, and Protein Adduction
Rudolph, V., Schopfer, F. J., Khoo, N. K. H., Rudolph, T. K., Cole, M. P., Woodcock, S. R., Bonacci, G., Groeger, A. L., Golin-Bisello, F., Chen, C.-S., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802298200 · Cited by 115 · see citing works
Self-citationJansson, E. Å., Petersson, J., Reinders, C., Sobko, T., Björne, H., Phillipson, M., Weitzberg, E., Holm, L., & Lundberg, J. O. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.11.018 · Cited by 106 · see citing works
Self-citationSchopfer, F. J., Batthyany, C., Baker, P. R. S., Bonacci, G., Cole, M. P., Rudolph, V., Groeger, A. L., Rudolph, T. K., Nadtochiy, S., Brookes, P. S., et al. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.12.025 · Cited by 104 · see citing works
Characterization of linoleic acid nitration in human blood plasma by mass spectrometry
Lima, É. S., Di Mascio, P., Rubbo, H., & Abdalla, D. S. P. (2002) · Biochemistry · doi:10.1021/bi025504j · Cited by 103 · see citing works
The PPARγ Agonist Rosiglitazone Impairs Colonic Inflammation in Mice with Experimental Colitis
Ramakers, J. D., Verstege, M. I., Thuijls, G., et al. (2007) · Journal of Clinical Immunology · doi:10.1007/s10875-007-9074-2 · Cited by 95 · see citing works
Nitric oxide and inflammation: The answer is blowing in the wind
Lundberg, J. O., Lundberg, J. M., Alving, K., & Weitzberg, E. (1997) · Nature Medicine · doi:10.1038/nm0197-30 · Cited by 70 · see citing works
Self-citationInsights into PPARγ from structures with endogenous and covalently bound ligands
Nettles, K. W. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb0908-893 · Cited by 32 · see citing works
Significance of anti-inflammatory effects of PPARγ agonists?
Rogler, G. (2006) · Gut · doi:10.1136/gut.2005.089946 · Cited by 20 · see citing works
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Larsen, F. J., Schiffer, T. A., Borniquel, S., Sahlin, K., Ekblom, B., Lundberg, J. O., & Weitzberg, E. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.004 · Cited by 689 · see citing works
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Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Espey, M. G. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.10.554 · Cited by 396 · see citing works
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Schopfer, F. J., Cipollina, C., & Freeman, B. A. (2011) · Chemical Reviews · doi:10.1021/cr200131e · Cited by 299 · see citing works
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Lundberg, J. O., & Weitzberg, E. (2013) · Gut · doi:10.1136/gutjnl-2011-301649 · Cited by 200 · see citing works
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Adamson, S., & Leitinger, N. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834a97e4 · Cited by 154 · see citing works
Conjugated linoleic acid is a preferential substrate for fatty acid nitration
Bonacci, G., Baker, P. R. S., Salvatore, S. R., Shores, D., Khoo, N. K. H., Koenitzer, J. R., Vitturi, D. A., Woodcock, S. R., Golin-Bisello, F., Cole, M. P., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.401356 · Cited by 147 · see citing works
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Self-citationS. Rocha, B., Gago, B., Pereira, C., M. Barbosa, R., Bartesaghi, S., O. Lundberg, J., Radi, R., & Laranjinha, J. (2011) · Current Drug Targets · doi:10.2174/138945011796150334 · Cited by 64 · see citing works
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Reddy, A. T., Lakshmi, S. P., Dornadula, S., Pinni, S., Rampa, D. R., & Reddy, R. C. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300730 · Cited by 42 · see citing works
Narala, V. R., Subramani, P. A., Narasimha, V. R., Shaik, F. B., & Panati, K. (2014) · International Immunopharmacology · doi:10.1016/j.intimp.2014.09.009 · Cited by 33 · see citing works
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- Authors
- Borniquel, S., Jansson, E. Å., Cole, M. P., Freeman, B. A., & Lundberg, J. O.
- Affiliations
- Karolinska Institutet (SE)
- University of Pittsburgh (US)
- Corresponding author
- Lundberg, Jon O.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 48
- Issue
- 4
- Pages
- 499-505
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC3290869
- OpenAlex
- W2058502722
- Cited by
- 92
- References
- 35
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 11 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 2 · 2016: 7 · 2015: 8 · 2014: 5 · 2013: 8 · 2012: 10
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL64937, R01HL064937, R37HL058115, R01HL058115, R01-HL-58115)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007052)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- nitro-fatty acids, PPARγ, inflammatory bowel disease, colitis, DSS-induced colitis, nitric oxide, 5-aminosalicylic acid, GW9662, colonic inflammation, anti-inflammatory signaling
- MeSH terms
- Animals, Fatty Acids, Female, Free Radicals, Mice, Inbred BALB C, Models, Biological, Nitric Oxide, Inflammatory Bowel Diseases, Up-Regulation, Gene Expression Regulation, Enzymologic, Cell Culture Techniques, Oleic Acid, Mesalamine, PPAR gamma, Mice
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