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. 2009 Jul 23;6(7):2055–2075. doi: 10.3390/ijerph6072055

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© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).

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Figure 7. — Liver-brain axis of neurodegeneration—Hypothesis. Progressive hepatic steatosis incites inflammation and pro-inflammatory cytokine activation. Attendant insulin resistance initiates a lipolysis and lipid disequilibrium cascade, leading to increased production and accumulation of ceramides. Ceramides are cytotoxic and promote insulin resistance, and their lipid solubility enables ready transfer across the blood-brain barrier to cause CNS insulin resistance and neurodegeneration with loss of neurons and oligodendrocytes. Ethanol’s lipid solubility enables it to exert direct neurotoxic effects, and cause brain insulin resistance.