The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Molecular Mechanisms of Lipotoxicity in Nonalcoholic Fatty Liver Disease
Open accessAbstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by insulin resistance, which results in elevated serum concentration of free fatty acids (FFAs). Circulating FFAs provide the substrate for triacylglycerol formation in the liver, and may also be directly cytotoxic. Hepatocyte apoptosis is a key histologic feature of NAFLD, and correlates with progressive inflammation and fibrosis. The molecular pathways leading to hepatocyte apoptosis are not fully defined; however, recent studies suggest that FFA-induced apoptosis contributes to the pathogenesis of nonalcoholic steatohepatitis. FFAs directly engage the core apoptotic machinery by activating the proapoptotic protein Bax, in a c-jun N-terminal kinase-dependent manner. FFAs also activate the lysosomal pathway of cell death and regulate death receptor gene expression. The role of ER stress and oxidative stress in the pathogenesis of nonalcoholic steatohepatitis has also been described. Understanding the molecular mediators of liver injury should promote development of mechanism-based therapeutic interventions.
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JNK1 but not JNK2 promotes the development of steatohepatitis in mice
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“In murine methionine and choline deficient dietary model of steatohepatitis, JNK1 mediates the development of liver injury.(57) JNK2 may also be involved in steatohepatitis, but its function is not obvious in the presence of JNK1.”
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Cited by
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
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Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077
Decoding cell death signals in liver inflammation
Brenner, C., Galluzzi, L., Kepp, O., & Kroemer, G. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.033 · Cited by 1,022
Nonalcoholic 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
- Malhi, H., & Gores, G.
- Venue
- Seminars in Liver Disease
- Publisher
- Georg Thieme Verlag KG
- Published
- 2008-10-27
- Volume
- 28
- Issue
- 04
- Pages
- 360-369
- ISSN
- 0272-8087 (ISSN-L)
- 1098-8971
- OpenAlex
- W2067038570
- Cited by
- 538
- References
- 12
- FWCI
- 18.83
- Type
- journal article
- Language
- en
- Open access
- green
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