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http://purl.uniprot.org/citations/22936979http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22936979http://www.w3.org/2000/01/rdf-schema#comment"

Background

How signals from fatty acid metabolism are translated into changes in food intake remains unclear. Previously we reported that mice with a genetic inactivation of Acads (acyl-coenzyme A dehydrogenase, short-chain), the enzyme responsible for mitochondrial beta-oxidation of C4-C6 short-chain fatty acids (SCFAs), shift consumption away from fat and toward carbohydrate when offered a choice between diets. In the current study, we sought to indentify candidate genes and pathways underlying the effects of SCFA oxidation deficiency on food intake in Acads-/-mice.

Methodology/principal findings

We performed a transcriptional analysis of gene expression in brain tissue of Acads-/- and Acads+/+ mice fed either a high-fat (HF) or low-fat (LF) diet for 2 d. Ingenuity Pathway Analysis revealed three top-scoring pathways significantly modified by genotype or diet: oxidative phosphorylation, mitochondrial dysfunction, and CREB signaling in neurons. A comparison of statistically significant responses in HF Acads-/-vs. HF Acads+/+ (3917) and Acads+/+ HF vs. LF Acads+/+ (3879) revealed 2551 genes or approximately 65% in common between the two experimental comparisons. All but one of these genes were expressed in opposite direction with similar magnitude, demonstrating that HF-fed Acads-deficient mice display transcriptional responses that strongly resemble those of Acads+/+ mice fed LF diet. Intriguingly, genes involved in both AMP-kinase regulation and the neural control of food intake followed this pattern. Quantitative RT-PCR in hypothalamus confirmed the dysregulation of genes in these pathways. Western blotting showed an increase in hypothalamic AMP-kinase in Acads-/-mice and HF diet increased, a key protein in an energy-sensing cascade that responds to depletion of ATP.

Conclusions

Our results suggest that the decreased beta-oxidation of short-chain fatty acids in Acads-deficient mice fed HF diet produces a state of energy deficiency in the brain and that AMP-kinase may be the cellular energy-sensing mechanism linking fatty acid oxidation to feeding behavior in this model."xsd:string
http://purl.uniprot.org/citations/22936979http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0041709"xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/author"Volaufova J."xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/author"Kumar K.G."xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/author"Mynatt R.L."xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/author"Richards B.K."xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/author"Kruger C."xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/pages"e41709"xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/title"Brain transcriptional responses to high-fat diet in Acads-deficient mice reveal energy sensing pathways."xsd:string
http://purl.uniprot.org/citations/22936979http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/22936979http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22936979
http://purl.uniprot.org/citations/22936979http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22936979
http://purl.uniprot.org/uniprot/#_Q07417-mappedCitation-22936979http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22936979
http://purl.uniprot.org/uniprot/#_Q6LCR2-mappedCitation-22936979http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22936979
http://purl.uniprot.org/uniprot/Q07417http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/22936979
http://purl.uniprot.org/uniprot/Q6LCR2http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/22936979