Analysis of Global and Absorption, Distribution, Metabolism, and Elimination Gene Expression in the Progressive Stages of Human Nonalcoholic Fatty Liver Disease

0367248 - BC 2012 RIV US eng J - Journal Article
Lake, A.D. - Novák, Petr - Fisher, C.D. - Jackson, J.P. - Hardwick, R.N. - Billheimer, D.D. - Klimecki, W.T. - Cherrington, N.J.
Analysis of Global and Absorption, Distribution, Metabolism, and Elimination Gene Expression in the Progressive Stages of Human Nonalcoholic Fatty Liver Disease.
Drug Metabolism and Disposition. Roč. 39, č. 10 (2011), s. 1954-1960. ISSN 0090-9556. E-ISSN 1521-009X
Institutional research plan: CEZ:AV0Z50510513
Keywords : Steatosis * Steatohepatitis * Nonalcoholic fatty liver disease
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.733, year: 2011

Nonalcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that range from simple fatty liver to nonalcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of human NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism, and elimination (ADME) of drugs. Differential gene expression between three clinically defined pathological groups-normal, steatosis, and NASH-was analyzed.The results suggest that uptake transporter genes are coordinately targeted for down-regulation at the global level during the pathological development of NASH and that these patients may have decreased drug uptake capacity. This coordinated regulation of uptake transporter genes is indicative of a hepatoprotective mechanism acting to prevent accumulation of toxic intermediates in disease-compromised hepatocytes.
Permanent Link: http://hdl.handle.net/11104/0201992