The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Altered Constitutive Expression of Fatty Acid-metabolizing Enzymes in Mice Lacking the Peroxisome Proliferator-activated Receptor α (PPARα)
Open accessAbstract
Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the steroid/nuclear receptor superfamily and mediates the biological and toxicological effects of peroxisome proliferators. To determine the physiological role of PPARalpha in fatty acid metabolism, levels of peroxisomal and mitochondrial fatty acid metabolizing enzymes were determined in the PPARalpha null mouse. Constitutive liver beta-oxidation of the long chain fatty acid, palmitic acid, was lower in the PPARalpha null mice as compared with wild type mice, indicating defective mitochondrial fatty acid catabolism. In contrast, constitutive oxidation of the very long chain fatty acid, lignoceric acid, was not different between wild type and PPARalpha null mice, suggesting that constitutive expression of enzymes involved in peroxisomal beta-oxidation is independent of PPARalpha. Indeed, the PPARalpha null mice had normal levels of the peroxisomal acyl-CoA oxidase, bifunctional protein (hydratase + 3-hydroxyacyl-CoA dehydrogenase), and thiolase but lower constitutive expression of the D-type bifunctional protein (hydratase + 3-hydroxyacyl-CoA dehydrogenase). Several mitochondrial fatty acid metabolizing enzymes including very long chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, short chain-specific 3-ketoacyl-CoA thiolase, and long chain acyl-CoA synthetase are also expressed at lower levels in the untreated PPARalpha null mice, whereas other fatty acid metabolizing enzymes were not different between the untreated null mice and wild type mice. A lower constitutive expression of mRNAs encoding these enzymes was also found, suggesting that the effect was due to altered gene expression. In wild type mice, both peroxisomal and mitochondrial enzymes were induced by the peroxisome proliferator Wy-14,643; induction was not observed in the PPARalpha null animals. These data indicate that PPARalpha modulates constitutive expression of genes encoding several mitochondrial fatty acid-catabolizing enzymes in addition to mediating inducible mitochondrial and peroxisomal fatty acid beta-oxidation, thus establishing a role for the receptor in fatty acid homeostasis.
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.
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
Braissant, O., Foufelle, F., Scotto, C., Dauça, M., & Wahli, W. (1996) · Endocrinology · doi:10.1210/endo.137.1.8536636 · Cited by 2,217
Kliewer, S. A., Sundseth, S. S., Jones, S. A., Brown, P. J., Wisely, G. B., Koble, C. S., Devchand, P., Wahli, W., Willson, T. M., Lenhard, J. M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4318 · Cited by 2,164
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
Self-citationChanges in lipoprotein kinetics during therapy with fenofibrate and other fibric acid derivatives
Ginsberg, H. N. (1987) · The American Journal of Medicine · doi:10.1016/0002-9343(87)90873-4 · Cited by 32
Cited by
(1998) · PubMed · Cited by 2,737
The mechanisms of action of PPARs
Berger, J., & Moller, D. E. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104018 · Cited by 2,659
Targeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G., & Gonzalez, F. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00062-3 · Cited by 1,819
Self-citationTranscriptional paradigms in mammalian mitochondrial biogenesis and function
Scarpulla, R. C. (2008) · Physiological Reviews · doi:10.1152/physrev.00025.2007 · Cited by 1,666
Peroxisome proliferator–activated receptor α mediates the adaptive response to fasting
Kersten, S., Seydoux, J., Peters, J. M., Gonzalez, F. J., Desvergne, B., & Wahli, W. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6223 · Cited by 1,649
Self-citationPawlak, M., Lefebvre, P., & Staels, B. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.039 · Cited by 1,578
Vega, R. B., Huss, J. M., & Kelly, D. P. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1868-1876.2000 · Cited by 1,195
Peroxisome Proliferator-Activated Receptor Alpha Target Genes
Rakhshandehroo, M., Knoch, B., Müller, M., & Kersten, S. (2010) · PPAR Research · doi:10.1155/2010/612089 · Cited by 1,020
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962
Chinetti, G., Fruchart, J.-C., & Staels, B. (2000) · Inflammation Research · doi:10.1007/s000110050622 · Cited by 954
Leone, T. C., Weinheimer, C. J., & Kelly, D. P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7473 · Cited by 943
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
Mouse models in non‐alcoholic fatty liver disease and steatohepatitis research
Anstee, Q. M., & Goldin, R. D. (2006) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2006.00465.x · Cited by 714
Peroxisomes: A Nexus for Lipid Metabolism and Cellular Signaling
Lodhi, I. J., & Semenkovich, C. F. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.002 · Cited by 605
Peroxisome proliferator-activated receptors: insight into multiple cellular functions
Escher, P., & Wahli, W. (2000) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/s0027-5107(99)00231-6 · Cited by 491
Kersten, S., Mandard, S., Tan, N. S., Escher, P., Metzger, D., Chambon, P., Gonzalez, F. J., Desvergne, B., & Wahli, W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004029200 · Cited by 489
Self-citationCentral Role of Pparα–Dependent Hepatic Lipid Turnover in Dietary Steatohepatitis in Mice
Ip, E., Farrell, G. C., Robertson, G., Hall, P., Kirsch, R., & Leclercq, I. (2003) · Hepatology · doi:10.1053/jhep.2003.50307 · Cited by 476
Mitochondrial biogenesis and dynamics in the developing and diseased heart
Dorn, G. W., Vega, R. B., & Kelly, D. P. (2015) · Genes & Development · doi:10.1101/gad.269894.115 · Cited by 470
Norris, A. W., Chen, L., Fisher, S. J., Szanto, I., Ristow, M., Jozsi, A. C., Hirshman, M. F., Rosen, E. D., Goodyear, L. J., Gonzalez, F. J., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17305 · Cited by 417
Self-citationDjouadi, F., Weinheimer, C. J., Saffitz, J. E., Pitchford, C., Bastin, J., Gonzalez, F. J., & Kelly, D. P. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3949 · Cited by 410
Self-citationPPARs: diverse regulators in energy metabolism and metabolic diseases
Wang, Y.-X. (2010) · Cell Research · doi:10.1038/cr.2010.13 · Cited by 366
The role of PPARs in inflammation and immunity
Clark, R. B. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.71.3.388 · Cited by 337
Watanabe, K., Fujii, H., Takahashi, T., Kodama, M., Aizawa, Y., Ohta, Y., Ono, T., Hasegawa, G., Naito, M., Nakajima, T., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000248200 · Cited by 314
Self-citationMolecular Mechanisms of Alcoholic Fatty Liver
Purohit, V., Gao, B., & Song, B. (2009) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00827.x · Cited by 312
Kim, K. H., Shin, H., Kim, K., Choi, H. M., Rhee, S. H., Moon, H., Kim, H. H., Yang, U. S., Yu, D., & Cheong, J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.039 · Cited by 281
Ligand Selectivity of the Peroxisome Proliferator-Activated Receptor α
Lin, Q., Ruuska, S. E., Shaw, N. S., Dong, D., & Noy, N. (1999) · Biochemistry · doi:10.1021/bi9816094 · Cited by 263
Regulation of Lipid and Lipoprotein Metabolism by PPAR Activators
Gervois, P., Torra, I. P., Fruchart, J.-C., & Staels, B. (2000) · cclm · doi:10.1515/cclm.2000.002 · Cited by 249
Highly Purified Eicosapentaenoic Acid Treatment Improves Nonalcoholic Steatohepatitis
Tanaka, N., Sano, K., Horiuchi, A., Tanaka, E., Kiyosawa, K., & Aoyama, T. (2008) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31815591aa · Cited by 248
Self-citationPPAR-α–Null Mice Are Protected From High-Fat Diet–Induced Insulin Resistance
Guerre-Millo, M., Rouault, C., Poulain, P., André, J., Poitout, V., Peters, J. M., Gonzalez, F. J., Fruchart, J.-C., Reach, G., & Staels, B. (2001) · Diabetes · doi:10.2337/diabetes.50.12.2809 · Cited by 241
Self-citationHashimoto, T., Fujita, T., Usuda, N., Cook, W., Qi, C., Peters, J. M., Gonzalez, F. J., Yeldandi, A. V., Rao, M. S., & Reddy, J. K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.27.19228 · Cited by 241
Self-citationMitochondrial Uncoupling: A Key Contributor to Reduced Cardiac Efficiency in Diabetes
Boudina, S., & Abel, E. D. (2006) · Physiology · doi:10.1152/physiol.00008.2006 · Cited by 199
Acyl-CoA Dehydrogenase 9 Is Required for the Biogenesis of Oxidative Phosphorylation Complex I
Nouws, J., Nijtmans, L., Houten, S. M., van den Brand, M., Huynen, M., Venselaar, H., Hoefs, S., Gloerich, J., Kronick, J., Hutchin, T., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.08.002 · Cited by 190
The PPARα-Dependent Rodent Liver Tumor Response Is Not Relevant to Humans: Addressing Misconceptions
Corton, J. C., Peters, J. M., & Klaunig, J. E. (2018) · Archives of Toxicology · doi:10.1007/s00204-017-2094-7 · Cited by 175
Self-citationObesity, Peroxisome Proliferator-Activated Receptor, and Atherosclerosis in Type 2 Diabetes
Blaschke, F., Takata, Y., Caglayan, E., Law, R. E., & Hsueh, W. A. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000191663.12164.77 · Cited by 176
Kockx, M., Gervois, P. P., Poulain, P., Derudas, B., Peters, J. M., Gonzalez, F. J., Princen, H. M. G., Kooistra, T., & Staels, B. (1999) · Blood · doi:10.1182/blood.v93.9.2991 · Cited by 139
Self-citationYang, Q., Xie, Y., Alexson, S. E. H., Dean Nelson, B., & DePierre, J. W. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)00923-1 · Cited by 131
Lipid metabolism in peroxisomes in relation to human disease
Wanders, R. J. A., & Tager, J. M. (1998) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(98)00003-x · Cited by 122
Makowski, L., Noland, R. C., Koves, T. R., Xing, W., Ilkayeva, O. R., Muehlbauer, M. J., Stevens, R. D., & Muoio, D. M. (2009) · The FASEB Journal · doi:10.1096/fj.08-119420 · Cited by 113
Kaimoto, S., Hoshino, A., Ariyoshi, M., Okawa, Y., Tateishi, S., Ono, K., Uchihashi, M., Fukai, K., Iwai-Kanai, E., & Matoba, S. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00553.2016 · Cited by 103
Akiyama, T. E., Lambert, G., Nicol, C. J., Matsusue, K., Peters, J. M., Brewer, H. B., & Gonzalez, F. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312802200 · Cited by 97
Self-citationvan Vlies, N., Ferdinandusse, S., Turkenburg, M., Wanders, R. J. A., & Vaz, F. M. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.07.001 · Cited by 98
Peroxisomal multifunctional protein-2: The enzyme, the patients and the knockout mouse model.
Huyghe, S., Mannaerts, G. P., Baes, M., & Van Veldhoven, P. P. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2006.04.006 · Cited by 91
Malik, V. S., Chiuve, S. E., Campos, H., Rimm, E. B., Mozaffarian, D., Hu, F. B., & Sun, Q. (2015) · Circulation · doi:10.1161/circulationaha.114.014911 · Cited by 89
Savolainen, K., Kotti, T. J., Schmitz, W., Savolainen, T. I., Sormunen, R. T., Ilves, M., Vainio, S. J., Conzelmann, E., & Hiltunen, J. K. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh107 · Cited by 83
Tanaka, N., Zhang, X., Sugiyama, E., Kono, H., Horiuchi, A., Nakajima, T., Kanbe, H., Tanaka, E., Gonzalez, F. J., & Aoyama, T. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.07.031 · Cited by 78
Self-citationNielsen, R., Grøntved, L., Stunnenberg, H. G., & Mandrup, S. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02266-05 · Cited by 77
Jia, Y., Kim, S., Kim, J., Kim, B., Wu, C., Lee, J. H., Jun, H., Kim, N., Lee, D., & Lee, S. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400399 · Cited by 76
Role of peroxisome proliferator-activated receptor-α in fasting-mediated oxidative stress
Abdelmegeed, M. A., Moon, K.-H., Hardwick, J. P., Gonzalez, F. J., & Song, B.-J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.06.017 · Cited by 74
Self-citationNakamura, T., Ito, Y., Yanagiba, Y., Ramdhan, D. H., Kono, Y., Naito, H., Hayashi, Y., Li, Y., Aoyama, T., Gonzalez, F. J., et al. (2009) · Toxicology · doi:10.1016/j.tox.2009.09.004 · Cited by 57
Self-citationInsulin Regulation of Hepatic Lipid Homeostasis
Uehara, K., Santoleri, D., Whitlock, A. E. G., & Titchenell, P. M. (2023) · Comprehensive Physiology · doi:10.1002/cphy.c220015 · Cited by 49
Sugiyama, E., Ishikawa, Y., Li, Y., Kagai, T., Nobayashi, M., Tanaka, N., Kamijo, Y., Yokoyama, S., Hara, A., & Aoyama, T. (2008) · Life Sciences · doi:10.1016/j.lfs.2008.04.011 · Cited by 43
Self-citationDeminice, R., de Castro, G. S. F., Francisco, L. V., da Silva, L. E. C. M., Cardoso, J. F. R., Frajacomo, F. T. T., Teodoro, B. G., dos Reis Silveira, L., & Jordao, A. A. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2014.11.014 · Cited by 39
Nakagawa, T., Ramdhan, D. H., Tanaka, N., Naito, H., Tamada, H., Ito, Y., Li, Y., Hayashi, Y., Yamagishi, N., Yanagiba, Y., et al. (2012) · Archives of Toxicology · doi:10.1007/s00204-011-0704-3 · Cited by 33
Self-citationThe regulation of acyl-CoA dehydrogenases in adipose tissue by rosiglitazone.
Goetzman, E. S. (2009) · Obesity · doi:10.1038/oby.2008.467 · Cited by 17
Metadata
- Authors
- Aoyama, T., Peters, J. M., Iritani, N., Nakajima, T., Furihata, K., Hashimoto, T., & Gonzalez, F. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-03
- Volume
- 273
- Issue
- 10
- Pages
- 5678-5684
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2102106861
- Cited by
- 863
- References
- 5
- FWCI
- 13.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
