The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Leukotriene B4 Is a Physiologically Relevant Endogenous Peroxisome Proliferator-activated Receptor-α Agonist
Open accessAbstract
Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play central roles in metabolism and inflammation. Although a variety of compounds have been shown to activate PPARs, identification of physiologically relevant ligands has proven difficult. In silico studies of lipid derivatives reported here identify specific 5-lipoxygenase products as candidate physiologically relevant PPAR-alpha activators. Subsequent studies show both in vitro and in a murine model of inflammation that 5-lipoxygenase stimulation induces PPAR-alpha signaling and that this results specifically from production of the inflammatory mediator and chemoattractant leukotriene B(4) (LTB(4)). Activation of PPAR-alpha is a direct effect of intracellularly generated LTB(4) binding to the nuclear receptor and not of secreted LTB(4) acting via its cell-surface receptors. Activation of PPAR-alpha reduces secretion of LTB(4) by stimulating degradation of this fatty acid derivative. We also show that the LTB(4) precursors leukotriene A(4) (LTA(4)) and 5-hydroperoxyeicosatetrenoic acid (5-HPETE) activate PPAR-alpha but have no significant endogenous effect independent of conversion to LTB(4). We conclude that LTB(4) is a physiologically relevant PPAR-alpha activator in cells of the immune system. This, together with previous findings, demonstrates that different types of lipids serve as endogenous PPAR-alpha ligands, with the relevant ligand varying between functionally different cell types. Our results also support the suggestion that regulation of inflammation may involve balancing proinflammatory effects of LTB(4), exerted through cell-surface receptors, and anti-inflammatory effects exerted through PPAR-alpha activation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“the PPARα nuclear receptor was of prime interest because is an established modulator of lipid metabolism”
From Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy (2019) · cites this paper as [54]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
15-Deoxy-Δ12,14-Prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ
FORMAN, B. M., Tontonoz, P., Chen, J., Brun, R. P., Spiegelman, B. M., & Evans, R. M. (1995) · Cell · doi:10.1016/0092-8674(95)90193-0 · Cited by 2,857
Forman, B. M., Chen, J., & Evans, R. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4312 · Cited by 2,116
The PPARα–leukotriene B4 pathway to inflammation control
Devchand, P. R., Keller, H., Peters, J. M., Vazquez, M., Gonzalez, F. J., & Wahli, W. (1996) · Nature · doi:10.1038/384039a0 · Cited by 1,345
Krey, G. D., Braissant, O., L’Horset, F., Kalkhoven, E., Perroud, M., Parker, M. G., & Wahli, W. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.6.0007 · Cited by 1,230
Peters-Golden, M. L., & Henderson, W. R. (2007) · New England Journal of Medicine · doi:10.1056/nejmra071371 · Cited by 1,068
Poynter, M. E., & Daynes, R. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.32833 · Cited by 556
Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver
Chakravarthy, M. V., Lodhi, I. J., Yin, L., Malapaka, R. R. V., Xu, H. E., TURK, J. W., & Semenkovich, C. F. (2009) · Journal of End-to-End-testing · doi:10.1016/j.cell.2009.05.036 · Cited by 536
Hashimoto, T., Cook, W. S., Qi, C., Yeldandi, A. V., Reddy, J. K., & Rao, M. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910350199 · Cited by 450
Zoete, V., Grosdidier, A., & Michielin, O. A. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2007.01.007 · Cited by 361
Peroxisome Proliferator–Activated Receptors as Transcriptional Nodal Points and Therapeutic Targets
Brown, J. D., & Plutzky, J. (2007) · Circulation · doi:10.1161/circulationaha.104.475673 · Cited by 345
Flagged first, then by citations
Cited by
Sorted by citations
Eicosanoid storm in infection and inflammation
Dennis, E. A., & Norris, P. C. (2015) · Nature Reviews Immunology · doi:10.1038/nri3859 · Cited by 1,517
Molecular Actions of PPARα in Lipid Metabolism and Inflammation
Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00064 · Cited by 898
Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease
Haeggström, J. Z., & Funk, C. D. (2011) · Chemical Reviews · doi:10.1021/cr200246d · Cited by 875
PPARs at the crossroads of lipid signaling and inflammation
Wahli, W., & Michalik, L. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.05.001 · Cited by 692
Synopsis of arachidonic acid metabolism: A review
Hanna, V. S., & HAFEZ, E. A. A. (2018) · Journal of Advanced Research · doi:10.1016/j.jare.2018.03.005 · Cited by 614
PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice
Wang, Y., Nakajima, T., Gonzalez, F. J., & Tanaka, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062061 · Cited by 560
“For example, long-chain fatty acids (FAs) and eicosanoids are typical endogenous ligands for PPARα and PPARβ/δ [5,6], whereas PPARγ is activated by arachidonic acid metabolites, such as 5-oxo-15(S)-hydroxyeicosatetraenoic acid and 5-oxo-eicosatetraenoic acid [7,8].”
BackgroundSelf-regulation of the inflammatory response by peroxisome proliferator-activated receptors
Korbecki, J., Bobiński, R., & Dutka, M. (2019) · Inflammation Research · doi:10.1007/s00011-019-01231-1 · Cited by 415
Old and new generation lipid mediators in acute inflammation and resolution
Stables, M. J., & Gilroy, D. W. (2010) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.07.005 · Cited by 343
Regulation of Ketone Body Metabolism and the Role of PPARα
Grabacka, M., Pierzchalska, M., Dean, M., & Reiss, K. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122093 · Cited by 305
“Arachidonic acid derived inflammatory mediators, such as leukotrienes LTB4 and LTA4 are natural PPARα agonists [158].”
BackgroundNuclear receptors and nonalcoholic fatty liver disease
Cave, M. C., Clair, H. B., Hardesty, J., Falkner, K. C., Feng, W., Clark, B. J., Sidey, J., Shi, H., Aqel, B. A., McClain, C. J., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.03.002 · Cited by 292
Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα
Tahri-Joutey, M., Andreoletti, P., Surapureddi, S., Nasser, B., Cherkaoui‐Malki, M., & Latruffe, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168969 · Cited by 273
PPARs and lipid ligands in inflammation and metabolism
Harmon, G. S., Lam, M. T., & Glass, C. K. (2011) · Chemical Reviews · doi:10.1021/cr2001355 · Cited by 216
Targeting nuclear receptors for the treatment of fatty liver disease
Tanaka, N., Aoyama, T., Kimura, S., & Gonzalez, F. J. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.05.011 · Cited by 217
“Long-chain FAs and eicosanoids are typical endogenous ligands for PPARα and PPARβ/δ (Narala et al., 2010; Yu et al., 1995), while PPARγ is specifically activated by arachidonic acid metabolites belonging to 5-hydroxyeicosatetraenoic acid family, such as 5-oxo-15(S)-hydroxyeicosatetraenoic acid and…”
BackgroundInfluentialParlati, L., Régnier, M., Guillou, H., & Postic, C. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100346 · Cited by 201
Endogenous Ligands for Nuclear Receptors: Digging Deeper
Schupp, M., & Lazar, M. A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r110.182451 · Cited by 183
Lipid Mediators in Inflammation
Bennett, M., & Gilroy, D. W. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.mchd-0035-2016 · Cited by 195
“16 through ligation to PPAR-α in its parent cell (155).”
BackgroundInfluentialSpite, M. R., Hellmann, J. L., Tang, Y., Mathis, S., Kosuri, M., Bhatnagar, A., Jala, V. R., & Haribabu, B. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100196 · Cited by 182
Leukotriene B 4 antagonism ameliorates experimental lymphedema
Tian, W., Rockson, S. G., Jiang, X., Kim, J., Begaye, A., Shuffle, E. M., Tu, A. B., Cribb, M., Nepiyushchikh, Z., Feroze, A. H., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal3920 · Cited by 173
Self-citationFibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy
Nogueira-Recalde, U., Lorenzo-Gómez, I., Blanco, F. J., Loza, M. I., Grassi, D., Shirinsky, V., Shirinsky, I., Lotz, M., Robbins, P. D., Domínguez, E., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.06.049 · Cited by 155
Obstructive sleep apnea and cognitive impairment: Addressing the blood–brain barrier
Lim, D. C., & Pack, A. I. (2013) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2012.12.003 · Cited by 158
Bäck, M., Dahlén, S., Drazen, J. M., Evans, J. F., Serhan, C. N., Shimizu, T., Yokomizo, T., & Rovati, G. E. (2011) · Pharmacological Reviews · doi:10.1124/pr.110.004184 · Cited by 160
Eicosanoids and Their Drugs in Cardiovascular Diseases: Focus on Atherosclerosis and Stroke
Capra, V., Bäck, M., Barbieri, S. S., Camera, M., Tremoli, E., & Rovati, G. E. (2012) · Medicinal Research Reviews · doi:10.1002/med.21251 · Cited by 118
Leukotriene modifiers for asthma treatment
Montuschi, P., & Peters-Golden, M. L. (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03630.x · Cited by 113
The role of the LTB4-BLT1 axis in health and disease
He, R., Chen, Y., & Cai, Q. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104857 · Cited by 115
Emerging anti-inflammatory strategies for COPD
Cazzola, M., Page, C. P., Calzetta, L., & Matera, M. G. (2012) · European Respiratory Journal · doi:10.1183/09031936.00213711 · Cited by 107
Wejksza, K., Lee-Chang, C., Bodogai, M., Bonzo, J. A., Gonzalez, F. J., Lehrmann, E., Becker, K. G., & Biragyn, A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201920 · Cited by 110
“The 5-LO pathway metabolites, in particular LTB4, induce and amplify local inflammation by controlling peroxisome proliferator– activated receptor a (PPARa) (10, 11).”
BackgroundInfluentialKarlsson, T., Turkina, M. V., Yakymenko, O., Magnusson, K., & Vikström, E. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002953 · Cited by 97
“It has, for example, been shown that different types of lipids, such as leukotriene B4, can bind to both cell-surface LTB4 receptor and nuclear PPAR ligands [56] to mediate pro-inflammatory events, such as chemotaxis and chemokinesis.”
BackgroundEicosanoids in Metabolic Syndrome
Hardwick, J. P., Eckman, K., Lee, Y., Abdelmegeed, M. A., Esterle, A. R., Chilian, W. M., Chiang, J. Y. L., & Song, B. (2013) · Advances in pharmacology · doi:10.1016/b978-0-12-404717-4.00005-6 · Cited by 97
“Activation of PPARα has several antiinflammatory properties that include induction of peroxisome β-oxidation and inactivation of eicosanoids (Narala et al., 2010), induction of I-κβ that blocks NF-κβ transcription of proinflammatory genes, increased expression of soluble interleukin-1 receptor…”
BackgroundMandard, S., & Patsouris, D. (2013) · PPAR Research · doi:10.1155/2013/613864 · Cited by 84
Identification and characterization of PPARα ligands in the hippocampus
Roy, A., Kundu, M., Jana, M., Mishra, R. K., Yung, Y. P., Luan, C.-H., Gonzalez, F. J., & Pahan, K. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2204 · Cited by 84
Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells
Gaida, M. M., Dapunt, U., & Hänsch, G. M. (2016) · Pathogens and Disease · doi:10.1093/femspd/ftw004 · Cited by 82
Nakamura, M., & Shimizu, T. (2011) · Chemical Reviews · doi:10.1021/cr100392s · Cited by 82
Duszka, K., Gregor, A., Guillou, H., König, J. S., & Wahli, W. (2020) · Cells · doi:10.3390/cells9071708 · Cited by 86
Kilaru, A., & Chapman, K. D. (2020) · Essays in Biochemistry · doi:10.1042/ebc20190086 · Cited by 81
PPARs: Key Regulators of Airway Inflammation and Potential Therapeutic Targets in Asthma
Banno, A., Reddy, A. T., Lakshmi, S. P., & Reddy, R. C. (2018) · Nuclear Receptor Research · doi:10.11131/2018/101306 · Cited by 68
“In chronic inflammatory conditions, such as those characterized by constitutive NF𝜅B activation and elevated levels of pro-inflammatory cytokines, WY-14643 treatment similarly suppresses TNF-𝛼 and IL-6 production [38].”
InfluentialPPAR-alpha in cutaneous inflammation
Dubrac, S., & Schmuth, M. (2011) · Dermato-Endocrinology · doi:10.4161/derm.3.1.14615 · Cited by 68
The role of the LTB 4 -BLT1 axis in chemotactic gradient sensing and directed leukocyte migration
Subramanian, B. C., Majumdar, R., & Parent, C. A. (2017) · Seminars in Immunology · doi:10.1016/j.smim.2017.07.002 · Cited by 68
“In silico docking studies suggests that LTB4 and other AA metabolites, such as 5-HpETE and LTA4, can directly bind to PPARα and can mediate PPARα action on the transcription of target genes [77].”
BackgroundGrabacka, M., Pierzchalska, M., & Reiss, K. (2013) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201011314030009 · Cited by 61
“This negative feedback loop is a part of inflammation resolution process [27, 28].”
BackgroundPPAR Agonists for the Prevention and Treatment of Lung Cancer
Lakshmi, S. P., Reddy, A. T., Banno, A., & Reddy, R. C. (2017) · PPAR Research · doi:10.1155/2017/8252796 · Cited by 61
Sanchez‐Covarrubias, L., Slosky, L. M., Thompson, B. J., Zhang, Y., Laracuente, M., DeMarco, K. M., Ronaldson, P. T., & Davis, T. P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088516 · Cited by 54
Bock, K. W. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.04.020 · Cited by 56
Søderstrøm, S., Lille‐Langøy, R., Yadetie, F., Rauch, M., Milinski, A., Dejaegere, A. P., Stote, R. H., Goksøyr, A., & Karlsen, O. A. (2022) · Environment International · doi:10.1016/j.envint.2022.107203 · Cited by 56
Basic aspects of tumor cell fatty acid-regulated signaling and transcription factors
Comba, A., Lin, Y., Eynard, A. R., Valentich, M. A., Fernández-Zapico, M. E., & Pasqualini, M. E. (2011) · Cancer and Metastasis Reviews · doi:10.1007/s10555-011-9308-x · Cited by 50
PPAR-γ Agonists and Their Role in Primary Cicatricial Alopecia
Harnchoowong, S., & Suchonwanit, P. (2017) · PPAR Research · doi:10.1155/2017/2501248 · Cited by 51
PPARα at the crossroad of metabolic–immune regulation in cancer
Zeng, W., Yin, X., Jiang, Y., Jin, L., & Liang, W. P. (2021) · FEBS Journal · doi:10.1111/febs.16181 · Cited by 52
Bock, K. W. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.07.009 · Cited by 50
Loss of 5‐lipoxygenase activity protects mice against paracetamol‐induced liver toxicity
Pu, S., Ren, L., Liu, Q., Kuang, J., Shen, J., Cheng, S., Zhang, Y., Jiang, W., Zhang, Z., Jiang, C., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13336 · Cited by 53
“Among their products, LTB4 and 8(S)-HETE are endogenous agonists for PPARα, and 12(S)HETE and 15(S)-HETE activate PPARγ (Muga et al., 2000; Narala et al., 2010; Sun et al., 2015).”
BackgroundFormation of lipoxins and resolvins in human leukocytes
Kahnt, A. S., Schebb, N. H., & Steinhilber, D. (2023) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2023.106726 · Cited by 54
Bervejillo, M. L., & Ferreira, A. M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-11488-6_3 · Cited by 50
Korbecki, J., Rębacz‐Maron, E., Kupnicka, P., Chlubek, D., & Baranowska‐Bosiacka, I. (2023) · Cancers · doi:10.3390/cancers15030946 · Cited by 44
“These prostaglandins are inhibitors of nuclear factor κB (NFκB) [6] and activators of PPARα and PPARγ [7,43]; thus, they have anti-inflammatory and anti-tumor properties.”
BackgroundInfluentialThe emerging role of PPAR-alpha in breast cancer
Qian, Z., Chen, L., Liu, J., Jiang, Y., & Zhang, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114420 · Cited by 42
Atherosclerosis: An Epigenetic Balancing Act that Goes Wrong
Lund, G., & Zaina, S. (2011) · Current Atherosclerosis Reports · doi:10.1007/s11883-011-0174-3 · Cited by 44
Targeting PPARβ/δ for the treatment of type 2 diabetes mellitus
Salvadó, L., Serrano, L., Barroso, E., Palomer, X., & Vázquez‐Carrera, M. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2012.658370 · Cited by 42
“Although most of the antiinflammatory effects of PPARs can be explained by transrepression, anti-inflammatory activities based on direct gene regulation through the PPARa-leukotriene B4 pathway [18,19] or by regulating IkBa expression [20] have also been described.”
BackgroundLopes, D. E. M., Jabr, C. L., Dejani, N. N., Saraiva, A. C., de Aquino, S. G., de Medeiros, A. I., & Rossa, C. (2017) · Journal of Periodontology · doi:10.1902/jop.2017.170210 · Cited by 39
Duszka, K., & Wahli, W. (2020) · Nutrients · doi:10.3390/nu12113476 · Cited by 37
“Moreover, inflammatory eicosanoids including prostaglandins and leukotrienes act as ligands for PPARs [568,569].”
BackgroundMartínez, N., Kurtz, M., Capobianco, E., Higa, R., White, V., & Jawerbaum, A. (2011) · Journal of Molecular Endocrinology · doi:10.1530/jme-10-0173 · Cited by 37
Martínez, N., White, V., Kurtz, M., Higa, R., Capobianco, E., & Jawerbaum, A. (2010) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.1151 · Cited by 36
Peripheral mechanisms of burn injury-associated pain
Laycock, H. C., Valente, J. D. S., Bantel, C., & Nagy, I. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.01.071 · Cited by 36
“In addition to BLT1 and TRPV1, LTB4 may also act on primary sensory neurons through the peroxisome proliferator-activated receptor α (LoVerme et al., 2006; Narala et al., 2010).”
BackgroundZhang, H., Wen, J., Zhang, Y.-N., Limbu, S. M., Du, Z., Qin, J. G., & Chen, L. (2018) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2018.12.011 · Cited by 34
Hole, C., Dhamsania, A., Brown, C., & Ryznar, R. J. (2025) · Cells · doi:10.3390/cells14080607 · Cited by 37
“This mechanism has been demonstrated in studies with PPAR-α knockout mice, which experienced excessive in fl ammation due to LTB4/5-LOX activation, a process that was a tt enu-ated with PPAR overexpression in transfected cells [87].”
Nutrient-dependent phosphorylation channels lipid synthesis to regulate PPARα
Jensen-Urstad, A. P. L., Song, H., Lodhi, I. J., Funai, K., Yin, L., Coleman, T., & Semenkovich, C. F. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m036103 · Cited by 32
Intermittent fasting—the future treatment in NASH patients?
Minciună, I., Gallage, S., Heikenwälder, M. F., Zelber‐Sagi, S., & Dufour, J. (2023) · Hepatology · doi:10.1097/hep.0000000000000330 · Cited by 31
Sharma-Walia, N., Chandran, K., Patel, K., Veettil, M. V., & Marginean, A. (2013) · Journal of Virology · doi:10.1128/jvi.02786-13 · Cited by 29
“5LO is a lipid-metabolizing enzyme (60, 81), and LTB4 activates transcription factor NF- B and PPARs, which play significant roles in lipid metabolism and cancer (117).”
BackgroundAdiponectin and Asthma: Knowns, Unknowns and Controversies
Oțelea, M. R., Arghir, O. C., Zugravu, C., & Rașcu, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168971 · Cited by 31
“Another presumptive action of ADPN in neutrophilic asthma would be the PPARα blockade of LTB4 [60].”
BackgroundInfluentialDubrac, S., Elentner, A., Schoonjans, K., Auwerx, J. H., & Schmuth, M. (2011) · European Journal of Immunology · doi:10.1002/eji.201041357 · Cited by 26
Interactions of PPAR-alpha and adenosine receptors in hypoxia-induced angiogenesis
Rizvi, Y. Q., Mehta, C. S., & Oyekan, A. (2013) · Vascular Pharmacology · doi:10.1016/j.vph.2013.09.001 · Cited by 26
Acyloxyacyl hydrolase modulates depressive-like behaviors through aryl hydrocarbon receptor
Aguiniga, L. M., Yang, W., Yaggie, R. E., Schaeffer, A. J., & Klumpp, D. J. (2019) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00029.2019 · Cited by 26
Kahle, N. A., Brenner‐Weiß, G., Overhage, J., Obst, U., & Hänsch, G. M. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.02.004 · Cited by 25
Emerging drugs for chronic obstructive pulmonary disease
Matera, M. G., Calzetta, L., Segreti, A., & Cazzola, M. (2012) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2012.660917 · Cited by 25
“Activation of PPARg and PPARa may have anti-inflammatory and immunomodulatory effects [71,72].”
BackgroundNeutrophils secrete exosome-associated DNA to resolve sterile acute inflammation
Arya, S. B., Collie, S. P., Xu, Y., Fernandez, M., Sexton, J. Z., Mosalaganti, S., Coulombe, P. A., & Parent, C. A. (2025) · Nature Cell Biology · doi:10.1038/s41556-025-01671-4 · Cited by 25
“90), a PPARα-specific antagonist 91 , to mouse dorsal ear skin 6 h post-TPA treatment in PBS-injected mice results in a defective clearance of infiltrated neutrophils 24 h after TPA treatment (Fig.”
InfluentialKajita, D., Nakamura, M., Matsumoto, Y., Ishikawa, M., Hashimoto, Y., & Fujii, S. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.05.045 · Cited by 23
Kurtz, M., Capobianco, E., Careaga, V. P., Martínez, N., Mazzucco, M. B., Maier, M., & Jawerbaum, A. (2014) · Journal of Endocrinology · doi:10.1530/joe-13-0362 · Cited by 22
“…leukotriene B4 (LTB4) is an endogenous ligand of PPARa, a PPAR isotype clearly involved in the oxidation of lipids in metabolic tissues http://joe.endocrinology-journals.org 2014 Society for Endocrinology DOI: 10.1530/JOE-13-0362 Printed in Great Britain (Lefebvre et al. 2006, Narala et al. 2010).”
BackgroundInfluentialTargeting Host Cellular Factors as a Strategy of Therapeutic Intervention for Herpesvirus Infections
Asha, K., & Sharma-Walia, N. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.603309 · Cited by 20
Temperilli, F., Franco, M. D., Massimi, I., Guarino, M. L., Guzzo, M. P., Valesini, G., Frati, L., & Pulcinelli, F. M. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.06.016 · Cited by 20
Essential Roles of PPARs in Lipid Metabolism during Mycobacterial Infection
Tanigawa, K., Luo, Y., Kawashima, A., Kiriya, M., Nakamura, Y., Karasawa, K., & Suzuki, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147597 · Cited by 22
“PPAR-β/δ agonists seem to have similar effects as PPAR-α and PPAR-γ agonists by increasing plasma HDL levels while lowering LDL.”
BackgroundInfluentialWang, W., Yang, L., Li, W., Sun, Y., Sun, H., Chen, Y., Ren, J., Guo, J., Wei, S., Lin, F., et al. (2025) · Chinese Medicine · doi:10.1186/s13020-025-01085-2 · Cited by 20
“Leukotriene B4 is a leukotriene related to inflammatory response, which can activate PPAR [35], participate in APOA2 mediated lipid transport and regulate energy metabolism [36].”
Vázquez, M. C., Rigotti, A., & Zanlungo, S. (2011) · Journal of Lipids · doi:10.1155/2012/547643 · Cited by 17
Nutrigenomic Functions of PPARs in Obesogenic Environments
Chung, S., Kim, Y. J., Yang, S. J., Lee, Y., & Lee, M. (2016) · PPAR Research · doi:10.1155/2016/4794576 · Cited by 19
Peroxisome Proliferator-Activated Receptors Features, Functions, and Future
Youssef, J., & Badr, M. Z. (2015) · Nuclear Receptor Research · doi:10.11131/2015/101188 · Cited by 16
Leukotriene Synthesis Is Critical for Medulloblastoma Progression
Du, F., Yuelling, L. W., Lee, E. H., Wang, Y., Liao, S., Cheng, Y. F., Zhang, L., Zheng, C., Peri, S., Cai, K. Q., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3549 · Cited by 16
“Previous studies have reported that leukotriene may function through the peroxisome proliferator activated receptors (PPAR), nuclear hormone receptors that act as ligand-activated transcription factors (48, 49).”
BackgroundReddy, A. T., Lakshmi, S. P., Banno, A., & Reddy, R. C. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00584 · Cited by 14
Lipid Mediators in Inflammation
Bennett, M., & Gilroy, D. W. (2017) · ASM Press eBooks · doi:10.1128/9781555819194.ch19 · Cited by 15
MK886 Reduces Cerebral Amyloid Angiopathy Severity in TgCRND8 Mice
Hawkes, C. A., Shaw, J. E., Brown, M., Sampson, A. P., McLaurin, J., & Carare, R. O. (2013) · Neurodegenerative Diseases · doi:10.1159/000351096 · Cited by 14
Is Fasting Good When One Is at Risk of Liver Cancer?
Minciună, I., van Kleef, L. A., Ştefănescu, H., & Procopeț, B. (2022) · Cancers · doi:10.3390/cancers14205084 · Cited by 13
Gallstone Disease and Its Correlation With Thyroid Disorders: A Narrative Review
Ravi, P. C., Thugu, T. R., Singh, J., Dasireddy, R. R., Kumar, S. A., Isaac, N. V., Oladimeji, A., DeTrolio, V. R., Abdalla, R., Mohan, V., et al. (2023) · Cureus · doi:10.7759/cureus.45116 · Cited by 14
“Numerous of these come from cholesterol [81].”
Wang, J., Zheng, S., Li, Z., Tang, Y., Huang, Y., Wang, J., Li, R., & Peng, J. (2024) · Food & Function · doi:10.1039/d4fo03970j · Cited by 13
Yang, H., Xiao, L., & Wang, N. (2016) · Journal of Diabetes · doi:10.1111/1753-0407.12506 · Cited by 13
“potential PPARα ligands, although at concentrations that were not adequate to characterize them as natural ligands.(52)”
BackgroundThomas, C. P., Tyrrell, V. J., Burston, J. J., Johnson, S. R. C., Aldrovandi, M., Álvarez-Jarreta, J., Inglis, R., Leonard, A., Fice, L., Costales, J., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2502640122 · Cited by 13
Neferine alleviates acute kidney injury by regulating the PPAR-α/NF-κB pathway
Xiong, Y., Zhong, J., Chen, W., Li, X., Liu, H. S., Li, Y., Xiong, W., & Li, H. (2024) · Clinical and Experimental Nephrology · doi:10.1007/s10157-024-02504-8 · Cited by 12
“Activation of PPAR-α by the endogenous ligand leukotriene B4 (LTB4) [27] enhances the expression of several downstream targets, including cytochrome P450 and β oxidase.”
Hanke, T., Lamers, C., Gomez, R. C., Schneider, G., Werz, O., & Schubert‐Zsilavecz, M. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.06.077 · Cited by 12
Saika, A., Tiwari, P., Nagatake, T., Node, E., Hosomi, K., Honda, T., Kabashima, K., & Kunisawa, J. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1097955 · Cited by 11
“PPARα activation reduces LTB4 production and the further acceleration of LTB4 metabolism (Narala et al., 2010).”
BackgroundZubareva, O. E., Kharisova, A. R., Roginskaya, A. I., Kovalenko, A. A., Zakharova, M. V., Schwarz, A. P., Sinyak, D. S., & Zaitsev, A. V. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810015 · Cited by 12
“For instance, PPAR γ is activated by the prostaglandin PGJ2 [20], while PPAR α is activated by leukotriene B4 [21].”
BackgroundKurtz, M., Martínez, N., Capobianco, E., Higa, R., Fornes, D. D., White, V., & Jawerbaum, A. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.05.018 · Cited by 10
Application of PPAR Ligands and Nanoparticle Technology in Metabolic Steatohepatitis Treatment
Vu, H. T., Nguyen, V. D., Ikenaga, H., & Matsubara, T. (2024) · Biomedicines · doi:10.3390/biomedicines12081876 · Cited by 9
Subramani, P. A., Panati, K., & Narala, V. R. (2013) · Bioinformation · doi:10.6026/97320630009629 · Cited by 9
Kumar, S. N., Darvin, S. S., Toppo, E., Porchezhiyan, V., Pandikumar, P., Paulraj, M. G., & Savarimuthu Ignacimuthu, S. J. (2022) · Biocatalysis and Agricultural Biotechnology · doi:10.1016/j.bcab.2022.102312 · Cited by 6
Macrophage Metabolism at the Crossroad of Metabolic Diseases and Cancer
Yang, S., den Bossche, J. V., & Ramalho, T. R. D. O. (2020) · Immunometabolism · doi:10.20900/immunometab20200022 · Cited by 7
Editorial: Molecular eavesdropping: phagocytic cells spy on bacterial communication
Hänsch, G. M. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0711358 · Cited by 6
“That signaling molecules use different receptors and activation pathways depending on the target cells is not unprecedented: leukotriene B4, for example, uses a surface receptor to induce chemotaxis of neutrophils but an intracellular receptor (PPAR ) to modify other cellular responses [15].”
BackgroundKim, E. Y., & Lee, J. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125825 · Cited by 7
Li, D., & Zhang, X. (2025) · Hepatology Communications · doi:10.1097/hc9.0000000000000846 · Cited by 8
“[131] 134] Dietary modification Dietary patterns consist of a complex combination of foods, nutrients, and beverages.”
Metadata
- Authors
- Narala, V. R., Adapala, R. K., Suresh, M. V., Brock, T. G., Peters-Golden, M., & Reddy, R. C.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Reddy, Raju C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 285
- Issue
- 29
- Pages
- 22067-22074
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2903376
- OpenAlex
- W2086928559
- Cited by
- 126
- References
- 29
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 10 · 2022: 4 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 8 · 2014: 4 · 2013: 13 · 2012: 12
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL-093196, R01HL093196)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- leukotriene B4, PPARα, 5-lipoxygenase, leukotriene A4, inflammation, eicosanoids, nuclear receptor signaling, immune cells
- MeSH terms
- Amino Acids, Animals, Arachidonate 5-Lipoxygenase, Cell Line, Humans, Leukotriene B4, Ligands, Models, Molecular, Computational Biology, PPAR alpha, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
