The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Specific Contribution of Methionine and Choline in Nutritional Nonalcoholic Steatohepatitis
Open accessAbstract
The pathogenesis and treatment of nonalcoholic steatohepatitis (NASH) are not well established. Feeding a diet deficient in both methionine and choline (MCD) is one of the most common models of NASH, which is characterized by steatosis, mitochondrial dysfunction, hepatocellular injury, oxidative stress, inflammation, and fibrosis. However, the individual contribution of the lack of methionine and choline in liver steatosis, advanced pathology and impact on mitochondrial S-adenosyl-L-methionine (SAM) and glutathione (GSH), known regulators of disease progression, has not been specifically addressed. Here, we examined the regulation of mitochondrial SAM and GSH and signs of disease in mice fed a MCD, methionine-deficient (MD), or choline-deficient (CD) diet. The MD diet reproduced most of the deleterious effects of MCD feeding, including weight loss, hepatocellular injury, oxidative stress, inflammation, and fibrosis, whereas CD feeding was mainly responsible for steatosis, characterized by triglycerides and free fatty acids accumulation. These findings were preceded by MCD- or MD-mediated SAM and GSH depletion in mitochondria due to decreased mitochondrial membrane fluidity associated with a lower phosphatidylcholine/phosphatidylethanolamine ratio. MCD and MD but not CD feeding resulted in increased ceramide levels by acid sphingomyelinase. Moreover, GSH ethyl ester or SAM therapy restored mitochondrial GSH and ameliorated hepatocellular injury in mice fed a MCD or MD diet. Thus, the depletion of SAM and GSH in mitochondria is an early event in the MCD model of NASH, which is determined by the lack of methionine. Moreover, therapy using permeable GSH prodrugs may be of relevance in NASH.
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Citations
Cites
Nonalcoholic Fatty Liver Disease
Angulo, P. (2002) · New England Journal of Medicine · doi:10.1056/nejmra011775 · Cited by 5,228
Steatohepatitis: A tale of two “hits”?
Day, C. P., & James, O. F. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70599-2 · Cited by 4,285
Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH
Caballero, F., Fernández, A., De Lacy, A. M., Fernández-Checa, J. C., Caballería, J., & García-Ruiz, C. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2008.12.016 · Cited by 368
Self-citation
Cited by
The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016) · Metabolism · doi:10.1016/j.metabol.2015.12.012 · Cited by 3,119
Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis
Rolo, A. P., Teodoro, J. S., & Palmeira, C. M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.003 · Cited by 955
Role of Oxidative Stress in Pathophysiology of Nonalcoholic Fatty Liver Disease
Masarone, M., Rosato, V., Dallio, M., Gravina, A. G., Aglitti, A., Loguercio, C., Federico, A., & Persico, M. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/9547613 · Cited by 648
An improved mouse model that rapidly develops fibrosis in non‐alcoholic steatohepatitis
Matsumoto, M., Hada, N., Sakamaki, Y., Uno, A., Shiga, T., Tanaka, C., Ito, T., Katsume, A., & Sudoh, M. (2013) · International Journal of Experimental Pathology · doi:10.1111/iep.12008 · Cited by 523
Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease
Gentric, G., Maillet, V., Paradis, V., Couton, D., L’Hermitte, A., Panasyuk, G., Fromenty, B., Celton-Morizur, S., & Desdouets, C. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73957 · Cited by 240
Song, B.-J., Akbar, M., Abdelmegeed, M. A., Byun, K., Lee, B., Yoon, S. K., & Hardwick, J. P. (2014) · Redox Biology · doi:10.1016/j.redox.2014.10.004 · Cited by 123
In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal
Soret, P.-A., Magusto, J., Housset, C., & Gautheron, J. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm10010036 · Cited by 121
Montfort, C. V., Matias, N., Fernandez, A., Fucho, R., de la Rosa, L. C., Martinez-Chantar, M. L., Mato, J. M., Machida, K., Tsukamoto, H., Murphy, M. P., et al. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.05.024 · Cited by 83
Self-citationHsu, M.-J., Karkossa, I., Schäfer, I., Christ, M., Kühne, H., Schubert, K., Rolle-Kampczyk, U. E., Kalkhof, S., Nickel, S., Seibel, P., et al. (2020) · Biomedicines · doi:10.3390/biomedicines8090350 · Cited by 43
Fraser, D. A., Wang, X., Lund, J., Nikolić, N., Iruarrizaga-Lejarreta, M., Skjaeret, T., Alonso, C., Kastelein, J. J. P., Rustan, A. C., Kim, Y. O., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.12.004 · Cited by 41
Metadata
- Authors
- Caballero, F., Fernández, A., Matías, N., Martínez, L., Fucho, R., Elena, M., Caballeria, J., Morales, A., Fernández-Checa, J. C., & García-Ruiz, C.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 285
- Issue
- 24
- Pages
- 18528-18536
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2050612118
- Cited by
- 238
- References
- 3
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
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