Journal
BIOCHIMIE
Volume 116, Issue -, Pages 52-60Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2015.06.023
Keywords
LA; LPS; Liver-protective; Mitochondria; Mice
Categories
Funding
- National Basic Science Research Program (973 program) of China [2015CB150300]
- Special Fund for Agro-scientific Research in the Public Interest [201003011]
- Program for New Century Excellent Talents in University [NCET-12-0889]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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alpha-Lipoic acid (LA) has been demonstrated to be a key regulator of energy metabolism. However, whether LA can protect the liver from inflammation, as well as the underlying mechanism involved, are still largely unclear. In the present study, mice treated with lipopolysaccharide (LPS) and injected with LA were used as a model. Liver injury, energy metabolism and mitochondrial regulation were investigated to assess the protective effect of LA on the liver and explore the possible mechanisms involved. Our results showed that LA attenuated liver injury, as evidenced by the decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels after LA treatment compared with the LPS-treated group. The hepatic ATP and NADH levels, expression levels of most mitochondrial DNA (mtDNA)-encoded genes as well as mitochondrial complex I, IV and V activities were all significantly increased in the LA-treated group compared with the LPS-treated group. Levels of Sirt3 protein, which is essential for the regulation of mitochondrial metabolism, were also increased in the LA-treated group. Regarding the regulation of mtDNA-encoded genes expression, we observed no obvious change in the methylation status of the mtDNA D-loop region. However, compared to the LPS-treated group, LA treatment increased glucocorticoid receptor (GR) protein expression in the liver, as well as the level of GR occupancy on the mtDNA D-loop region. Our study demonstrates that LA exerts a liver-protective effect in an inflammation state by improving mitochondria( function. Furthermore, to the best of our knowledge, we demonstrate for the first time that GR may be involved in this effect via an enhanced binding to the mtDNA transcriptional control region, thereby regulating the expression of mtDNA-encoded genes. (C) 2015 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
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