Int. J. Environ. Res. Public Health 2009, 6(7), 2055-2075; doi:10.3390/ijerph6072055
Article

The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids

1,3-8,* email, 6,7email, 2,3,6,7,8email, 3,7,8email and 2,3,6,7,8email
1 Division of Neuropathology, Brown University, Providence, RI, USA 2 Division of Gastroenterology, Brown University, Providence, RI, USA 3 Department of Medicine, Brown University, Providence, RI, USA 4 Department of Pathology, Brown University, Providence, RI, USA 5 Department of Neurology, Brown University, Providence, RI, USA 6 The Liver Research Center, Brown University, Providence, RI, USA 7 Rhode Island Hospital, Brown University, Providence, RI, USA 8 The Warren Alpert Medical School, Brown University, Providence, RI, USA
* Author to whom correspondence should be addressed.
Received: 24 June 2009; Accepted: 16 July 2009 / Published: 23 July 2009
(This article belongs to the Special Issue Alcohol and Public Health)
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Abstract: Alcohol abuse causes progressive toxicity and degeneration in liver and brain due to insulin resistance, which exacerbates oxidative stress and pro-inflammatory cytokine activation. Alcohol-induced steatohepatitis promotes synthesis and accumulation of ceramides and other toxic lipids that cause insulin resistance. Ceramides can readily cross the blood-brain barrier, and ceramide exposure causes neurodegeneration with insulin resistance and oxidative stress, similar to the effects of alcohol. Therefore, in addition to its direct neurotoxic effects, alcohol misuse establishes a liver-brain axis of neurodegeneration mediated by toxic lipid trafficking across the blood-brain barrier, leading to progressive white matter degeneration and cognitive impairment.
Keywords: ethanol; insulin resistance; ceramides; neurodegeneration; alcoholic liver disease; steatohepatitis

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MDPI and ACS Style

De la Monte, S.M.; Longato, L.; Tong, M.; DeNucci, S.; Wands, J.R. The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids. Int. J. Environ. Res. Public Health 2009, 6, 2055-2075.

AMA Style

De la Monte SM, Longato L, Tong M, DeNucci S, Wands JR. The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids. International Journal of Environmental Research and Public Health. 2009; 6(7):2055-2075.

Chicago/Turabian Style

De la Monte, Suzanne M.; Longato, Lisa; Tong, Ming; DeNucci, Sarah; Wands, Jack R. 2009. "The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids." Int. J. Environ. Res. Public Health 6, no. 7: 2055-2075.

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