Role of mitochondria in non-alcoholic fatty liver disease
- PMID: 17567459
- DOI: 10.1111/j.1440-1746.2006.04640.x
Role of mitochondria in non-alcoholic fatty liver disease
Erratum in
- J Gastroenterol Hepatol. 2008 Mar;23(3):501-2
Abstract
Mitochondrial dysfunction is involved in the three stages of the transition from lack of exercise and excessive food intake to insulin resistance, diabetes and non-alcoholic steatohepatitis (NASH). In muscle, lack of exercise, a fat-rich diet, a polymorphism in peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), and possibly age-related mitochondrial DNA (mtDNA) mutations may variously combine their effects to decrease PGC-1 expression, mitochondrial biogenesis and fat oxidation. Together with excessive food intake, insufficient fat oxidation causes fat accumulation and cellular stress in myocytes. The activation of Jun N-terminal kinase and protein kinase C-theta triggers the serine phosphorylation and inactivation of the insulin receptor substrate, and hampers the insulin-mediated translocation of glucose transporter-4 to the plasma membrane. Initially, the trend for increased blood glucose increases insulin secretion by pancreatic beta-cells. High plasma insulin levels compensate for insulin resistance in muscle and maintain normal blood glucose levels. Eventually, however, increased uncoupling protein-2 expression and possibly acquired mtDNA mutations in pancreatic beta-cells can blunt glucose-mediated adenosine triphosphate (ATP) formation and insulin secretion, to cause diabetes in some patients. High plasma glucose and/or insulin levels induce hepatic lipogenesis and cause hepatic steatosis. In fat-engorged hepatocytes, several vicious cycles involving tumor necrosis factor-alpha, reactive oxygen species (ROS), peroxynitrite, and lipid peroxidation products alter respiratory chain polypeptides and mtDNA, thus partially blocking the flow of electrons in the respiratory chain. The overreduction of upstream respiratory chain complexes increases mitochondrial ROS and peroxynitrite formation. Oxidative stress increases the release of lipid peroxidation products and cytokines, which together trigger the liver lesions of NASH.
Similar articles
-
Alterations in hepatic mitochondrial compartment in a model of obesity and insulin resistance.Obesity (Silver Spring). 2008 May;16(5):958-64. doi: 10.1038/oby.2008.10. Epub 2008 Feb 14. Obesity (Silver Spring). 2008. PMID: 18277391
-
Mitochondrial involvement in non-alcoholic steatohepatitis.Mol Aspects Med. 2008 Feb-Apr;29(1-2):22-35. doi: 10.1016/j.mam.2007.09.014. Epub 2007 Nov 1. Mol Aspects Med. 2008. PMID: 18061659 Review.
-
Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents.Diabetes. 2007 Aug;56(8):2085-92. doi: 10.2337/db07-0093. Epub 2007 May 22. Diabetes. 2007. PMID: 17519422
-
[Role of oxidative stress in non-alcoholic steatohepatitis].Nihon Rinsho. 2006 Jun;64(6):1077-82. Nihon Rinsho. 2006. PMID: 16768112 Review. Japanese.
-
Nonalcoholic steatosis and steatohepatitis. V. Mitochondrial dysfunction in steatohepatitis.Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G193-9. doi: 10.1152/ajpgi.00426.2001. Am J Physiol Gastrointest Liver Physiol. 2002. PMID: 11804839 Review.
Cited by
-
Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness With Liver Fat Among Older Adults.J Gerontol A Biol Sci Med Sci. 2024 Apr 1;79(4):glae047. doi: 10.1093/gerona/glae047. J Gerontol A Biol Sci Med Sci. 2024. PMID: 38366047
-
Thyroid Hormone and Mitochondrial Dysfunction: Therapeutic Implications for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).Cells. 2023 Dec 9;12(24):2806. doi: 10.3390/cells12242806. Cells. 2023. PMID: 38132126 Free PMC article. Review.
-
Untargeted Metabolomics Identifies Biomarkers for MCADD Neonates in Dried Blood Spots.Int J Mol Sci. 2023 Jun 2;24(11):9657. doi: 10.3390/ijms24119657. Int J Mol Sci. 2023. PMID: 37298607 Free PMC article.
-
From Non-Alcoholic Fatty Liver to Hepatocellular Carcinoma: A Story of (Mal)Adapted Mitochondria.Biology (Basel). 2023 Apr 14;12(4):595. doi: 10.3390/biology12040595. Biology (Basel). 2023. PMID: 37106795 Free PMC article. Review.
-
The Non-Invasive Assessment of Circulating D-Loop and mt-ccf Levels Opens an Intriguing Spyhole into Novel Approaches for the Tricky Diagnosis of NASH.Int J Mol Sci. 2023 Jan 24;24(3):2331. doi: 10.3390/ijms24032331. Int J Mol Sci. 2023. PMID: 36768654 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous