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标题：Decreased body weight and hepatic steatosis with altered fatty acid ethanolamide metabolism in aged L-Fabp −/− mice
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作者：Elizabeth P. Newberry ; Susan M. Kennedy ; Yan Xie 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2012
卷号：53
期号：4
页码：744-754
DOI：10.1194/jlr.M020966
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The tissue-specific sources and regulated production of physiological signals that modulate food intake are incompletely understood. Previous work showed that L-Fabp ^−/− mice are protected against obesity and hepatic steatosis induced by a high-fat diet, findings at odds with an apparent obesity phenotype in a distinct line of aged L-Fabp ^−/− mice. Here we show that the lean phenotype in L-Fabp ^−/− mice is recapitulated in aged, chow-fed mice and correlates with alterations in hepatic, but not intestinal, fatty acid amide metabolism. L-Fabp ^−/− mice exhibited short-term changes in feeding behavior with decreased food intake, which was associated with reduced abundance of key signaling fatty acid ethanolamides, including oleoylethanolamide (OEA, an agonist of PPARα) and anandamide (AEA, an agonist of cannabinoid receptors), in the liver. These reductions were associated with increased expression and activity of hepatic fatty acid amide hydrolase-1, the enzyme that degrades both OEA and AEA. Moreover, L-Fabp ^−/− mice demonstrated attenuated responses to OEA administration, which was completely reversed with an enhanced response after administration of a nonhydrolyzable OEA analog. These findings demonstrate a role for L-Fabp in attenuating obesity and hepatic steatosis, and they suggest that hepatic fatty acid amide metabolism is altered in L-Fabp ^−/− mice.
关键词：fatty acid binding protein ; satiety ; obesity ; feeding behavior