Section 37
Chapter 36,165

Liver mitochondrial function and redox status in an experimental model of non-alcoholic fatty liver disease induced by monosodium L-glutamate in rats

Lazarin, M.d.O.; Ishii-Iwamoto, E.L.; Yamamoto, N.S.; Constantin, R.P.; Garcia, R.ân.F.; da Costa, C.íl.E.M.; Vitoriano, A.d.S.; de Oliveira, M.C.; Salgueiro-Pagadigorria, C.L.

Experimental and Molecular Pathology 91(3): 687-694


ISSN/ISBN: 1096-0945
PMID: 21821020
DOI: 10.1016/j.yexmp.2011.07.003
Accession: 036164498

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The purpose of this work was to determine if mitochondrial dysfunction is involved in the development of non-alcoholic fatty liver disease (NAFLD). Using a model of obesity induced by the neonatal treatment of rats with monosodium L-glutamate (MSG), several parameters of liver mitochondrial function and their impact on liver redox status were evaluated. Specifically, fatty acid β-oxidation, oxidative phosphorylation and Ca(2+)-induced mitochondrial permeability transition were assessed in isolated liver mitochondria, and reduced glutathione (GSH), linked thiol contents and the activities of several enzymes involved in the control of redox status were measured in the liver homogenate. Our results demonstrate that liver mitochondria from MSG-obese rats exhibit a higher β-oxidation capacity and an increased capacity for oxidising succinate, without loss in the efficiency of oxidative phosphorylation. Also, liver mitochondria from obese rats were less susceptible to the permeability transition pore (PTP) opening induced by 1.0 μM CaCl(2). Cellular levels of GSH were unaffected in the livers from the MSG-obese rats, whereas reduced linked thiol contents were increased. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase and glutathione peroxidase were increased, while catalase activity was unaffected and superoxide dismutase activity was reduced in the livers from the MSG-obese rats. In this model of obesity, liver fat accumulation is not a consequence of mitochondrial dysfunction. The enhanced glucose-6-phosphate dehydrogenase activity observed in the livers of MSG-obese rats could be associated with liver fat accumulation and likely plays a central role in the mitochondrial defence against oxidative stress.

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