The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress
Open accessAbstract
BACKGROUND: Uric acid is an independent risk factor in fructose-induced fatty liver, but whether it is a marker or a cause remains unknown. RESULTS: Hepatocytes exposed to uric acid developed mitochondrial dysfunction and increased de novo lipogenesis, and its blockade prevented fructose-induced lipogenesis. CONCLUSION: Rather than a consequence, uric acid induces fatty liver SIGNIFICANCE: Hyperuricemic people are more prone to develop fructose-induced fatty liver. Metabolic syndrome represents a collection of abnormalities that includes fatty liver, and it currently affects one-third of the United States population and has become a major health concern worldwide. Fructose intake, primarily from added sugars in soft drinks, can induce fatty liver in animals and is epidemiologically associated with nonalcoholic fatty liver disease in humans. Fructose is considered lipogenic due to its ability to generate triglycerides as a direct consequence of the metabolism of the fructose molecule. Here, we show that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that is triggered from the rapid phosphorylation of fructose by fructokinase. Generated AMP enters into the purine degradation pathway through the activation of AMP deaminase resulting in uric acid production and the generation of mitochondrial oxidants. Mitochondrial oxidative stress results in the inhibition of aconitase in the Krebs cycle, resulting in the accumulation of citrate and the stimulation of ATP citrate lyase and fatty-acid synthase leading to de novo lipogeneis. These studies provide new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states.
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Cites
Modified Reagents for Determination of Urea and Ammonia
Chaney, A. L., & Marbach, E. P. (1962) · Clinical Chemistry · doi:10.1093/clinchem/8.2.130 · Cited by 3,938
The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
Adams, L. A., Lymp, J. F., St. Sauver, J., Sanderson, S. O., Lindor, K. D., Feldstein, A., & Angulo, P. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.04.014 · Cited by 2,890
Uric Acid and Cardiovascular Risk
Feig, D. I., Kang, D.-H., & Johnson, R. J. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0800885 · Cited by 2,440
Self-citationMetabolic Effects of Fructose and the Worldwide Increase in Obesity
Tappy, L., & Lê, K.-A. (2010) · Physiological Reviews · doi:10.1152/physrev.00019.2009 · Cited by 1,256
A causal role for uric acid in fructose-induced metabolic syndrome
Nakagawa, T., Hu, H., Zharikov, S., Tuttle, K. R., Short, R. A., Glushakova, O., Ouyang, X., Feig, D. I., Block, E. R., Herrera-Acosta, J., et al. (2006) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00140.2005 · Cited by 1,104
Self-citationDrozdzowska, B., Pluskiewicz, W., Halaba, Z. P., Misiołek, H., & Beck, B. R. (2005) · Cited by 984
Feig, D. I., Soletsky, B., & Johnson, R. J. (2008) · JAMA · doi:10.1001/jama.300.8.924 · Cited by 914
Self-citationKang, D.-H., Park, S.-K., Lee, I.-K., & Johnson, R. J. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2005050572 · Cited by 882
Self-citationFructose consumption as a risk factor for non-alcoholic fatty liver disease
Ouyang, X., Cirillo, P., Sautin, Y., McCall, S., Bruchette, J. L., Diehl, A. M., Johnson, R. J., & Abdelmalek, M. F. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.02.011 · Cited by 863
Self-citationSautin, Y. Y., Nakagawa, T., Zharikov, S., & Johnson, R. J. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00600.2006 · Cited by 787
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Cited by
Mechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
The role of sugar-sweetened beverages in the global epidemics of obesity and chronic diseases
Malik, V. S., & Hu, F. B. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00627-6 · Cited by 854
Sugar, Uric Acid, and the Etiology of Diabetes and Obesity
Johnson, R. J., Nakagawa, T., Sanchez-Lozada, L. G., Shafiu, M., Sundaram, S., Le, M., Ishimoto, T., Sautin, Y. Y., & Lanaspa, M. A. (2013) · Diabetes · doi:10.2337/db12-1814 · Cited by 760
Self-citationRole of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease
Softic, S., Cohen, D. E., & Kahn, C. R. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4054-0 · Cited by 709
Fructose metabolism and metabolic disease
Hannou, S. A., Haslam, D. E., McKeown, N. M., & Herman, M. A. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96702 · Cited by 561
Metadata
- Authors
- Lanaspa, M. A., Sanchez-Lozada, L. G., Choi, Y.-J., Cicerchi, C., Kanbay, M., Roncal-Jimenez, C. A., Ishimoto, T., Li, N., Marek, G., Duranay, M., Schreiner, G., Rodriguez-Iturbe, B., Nakagawa, T., Kang, D.-H., Sautin, Y. Y., & Johnson, R. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 287
- Issue
- 48
- Pages
- 40732-40744
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2041572943
- Cited by
- 710
- References
- 53
- FWCI
- 13.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Lanaspa, M. A., Sanchez-Lozada, L. G., Choi, Y.-J., Cicerchi, C., Kanbay, M., Roncal-Jimenez, C. A., Ishimoto, T., Li, N., Marek, G., Duranay, M., Schreiner, G., Rodriguez-Iturbe, B., Nakagawa, T., Kang, D.-H., Sautin, Y. Y., & Johnson, R. J. (2012). Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m112.399899
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