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E-GEOD-30495

ABSTRACT: Gene expression profile of PPARalpha knockout and wild type mice after a single oral dose of different synthetic triglycerides

OTHER RELATED OMICS DATASETS IN: PRJNA154781PRJNA154763PRJNA144617

PROVIDER: E-GEOD-30495 | ExpressionAtlas | 2015-09-21

REPOSITORIES: ExpressionAtlas

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Project description:Fatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid. Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPARalpha-/- mice to allow exploration of the specific contribution of PPARalpha. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPARalpha agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPARalpha-dependent manner, emphasizing the importance of PPARalpha in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPARalpha had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPARalpha. To study the transcriptional effects of specific fatty acids in the intact heart, wild type and PPARalpha-/- mice were given a single oral dose of 4 synthetic triglycerides composed of one single fatty acid, as well as of the synthetic PPARalpha agonist Wy14,643. Hearts were collected 6h after gavag and used for whole genome gene expression profiling.

Dataset Information

E-GEOD-30495

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