The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a serious health problem. Although NAFLD represents a form of lipotoxicity, its pathogenesis remains poorly understood. The aim of this study was to examine the cellular mechanisms involved in free fatty acid (FFA)-mediated hepatic lipotoxicity. FFA treatment of liver cells resulted in Bax translocation to lysosomes and lysosomal destabilization with release of cathepsin B (ctsb), a lysosomal cysteine protease, into the cytosol. This process was also partially dependent on ctsb. Lysosomal destabilization resulted in nuclear factor κB-dependent tumor necrosis factor α expression. Release of ctsb into the cytoplasm was also observed in humans with NAFLD and correlated with disease severity. In a dietary murine model of NAFLD, either genetic or pharmacological inactivation of ctsb protected against development of hepatic steatosis, liver injury, and insulin resistance with its associated “dysmetabolic syndrome.” In conclusion, these data support a lipotoxic model of FFA-mediated lysosomal destabilization. Supplemental material for this article can be found on the Hepatology website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (Hepatology 2004;40:185-194.)
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Cites
Nonalcoholic Fatty Liver Disease
Angulo, P. (2002) · New England Journal of Medicine · doi:10.1056/nejmra011775 · Cited by 5,228
The Bcl2 family: regulators of the cellular life-or-death switch
Cory, S., & Adams, J. M. (2002) · Nature Reviews Cancer · doi:10.1038/nrc883 · Cited by 4,032
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.
MATTEONI, C., YOUNOSSI, Z., GRAMLICH, T., BOPARAI, N., LIU, Y., & MCCULLOUGH, A. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70506-8 · Cited by 3,345
Nonalcoholic Fatty Liver Disease
Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., & Melchionda, N. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1844 · Cited by 2,581
Yuan, M., Konstantopoulos, N., Lee, J., Hansen, L., Li, Z.-W., Karin, M., & Shoelson, S. E. (2001) · Science · doi:10.1126/science.1061620 · Cited by 1,884
Lipotoxic heart disease in obese rats: Implications for human obesity
Zhou, Y.-T., Grayburn, P., Karim, A., Shimabukuro, M., Higa, M., Baetens, D., Orci, L., & Unger, R. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1784 · Cited by 1,265
Fatty acid-induced β cell apoptosis: A link between obesity and diabetes
Shimabukuro, M., Zhou, Y.-T., Levi, M., & Unger, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2498 · Cited by 1,142
Unger, R. H. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104057 · Cited by 875
The role of TNFα and TNF receptors in obesity and insulin resistance
Hotamisligil, G. S. (1999) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1999.00490.x · Cited by 780
Cited by
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548
A lipidomic analysis of nonalcoholic fatty liver disease
Puri, P., Baillie, R. A., Wiest, M. M., Mirshahi, F., Choudhury, J., Cheung, O., Sargeant, C., Contos, M. J., & Sanyal, A. J. (2007) · Hepatology · doi:10.1002/hep.21763 · Cited by 1,338
Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077
Triggering and resolution of inflammation in NASH
Schuster, S., Cabrera, D., Arrese, M., & Feldstein, A. E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0009-6 · Cited by 943
Self-citationNonalcoholic Fatty Liver Disease: Pathology and Pathogenesis
Tiniakos, D. G., Vos, M. B., & Brunt, E. M. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102132 · Cited by 870
Metadata
- Authors
- Feldstein, A. E., Werneburg, N. W., Canbay, A., Guicciardi, M. E., Bronk, S. F., Rydzewski, R., Burgart, L. J., & Gores, G. J.
- Venue
- Hepatology
- Published
- 2004-07
- Volume
- 40
- Issue
- 1
- Pages
- 185-194
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1984077928
- Cited by
- 834
- References
- 11
- FWCI
- 18.23
- Type
- journal article
- Language
- en
- Open access
- closed
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- Feldstein, A. E., Werneburg, N. W., Canbay, A., Guicciardi, M. E., Bronk, S. F., Rydzewski, R., Burgart, L. J., & Gores, G. J. (2004). Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway. Hepatology. https://doi.org/10.1002/hep.20283
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