Abstract |
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 PPARĪ±) 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.
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Authors | Elizabeth P Newberry, Susan M Kennedy, Yan Xie, Jianyang Luo, Rosanne M Crooke, Mark J Graham, Jin Fu, Daniele Piomelli, Nicholas O Davidson |
Journal | Journal of lipid research
(J Lipid Res)
Vol. 53
Issue 4
Pg. 744-54
(Apr 2012)
ISSN: 1539-7262 [Electronic] United States |
PMID | 22327204
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Arachidonic Acids
- Endocannabinoids
- Fabp1 protein, mouse
- Fatty Acid-Binding Proteins
- Oleic Acids
- PPAR gamma
- Polyunsaturated Alkamides
- oleoylethanolamide
- Amidohydrolases
- fatty-acid amide hydrolase
- anandamide
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Topics |
- Adiposity
- Age Factors
- Amidohydrolases
(genetics, metabolism)
- Animals
- Arachidonic Acids
(administration & dosage, pharmacology)
- Body Weight
- Chromosomes
(genetics, metabolism)
- Diet, Fat-Restricted
- Endocannabinoids
- Enzyme Activation
- Fatty Acid-Binding Proteins
(genetics, metabolism)
- Fatty Liver
(genetics, pathology)
- Feeding Behavior
- Female
- Lipid Metabolism
- Liver
(drug effects, metabolism, pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Obesity
(metabolism, pathology)
- Oleic Acids
(administration & dosage, pharmacology)
- PPAR gamma
(genetics, metabolism)
- Polyunsaturated Alkamides
(administration & dosage, pharmacology)
- Quantitative Trait Loci
- Signal Transduction
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