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Insulin signaling regulates fatty acid catabolism at the level of CoA activation
German Cancer Research Center (DKFZ), Heidelberg, Germany.
VTT Technical Research Centre of Finland, Espoo, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
VTT Technical Research Centre of Finland, Espoo, Finland.
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2012 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 8, no 1, article id e1002478Article in journal (Refereed) Published
Abstract [en]

The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG) catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS). We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.

Place, publisher, year, edition, pages
Public Library of Science , 2012. Vol. 8, no 1, article id e1002478
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:oru:diva-63663DOI: 10.1371/journal.pgen.1002478ISI: 000300223400038PubMedID: 22275878Scopus ID: 2-s2.0-84857473501OAI: oai:DiVA.org:oru-63663DiVA, id: diva2:1169226
Funder
EU, FP7, Seventh Framework Programme
Note

Funding agencies:

Diabetes UK grant 06/0003416 Diabetes UK grant 06/0003416 

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-22Bibliographically approved

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Oresic, Matej

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