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Insulin signaling regulates fatty acid catabolism at the level of CoA activation

Xu, Xiaojun (författare)
German Cancer Research Center (DKFZ), Heidelberg, Germany
Gopalacharyulu, Peddinti (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Seppänen-Laakso, Tuulikki (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
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Ruskeepää, Anna-Liisa (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Aye, Cho Cho (författare)
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Carson, Brian P. (författare)
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Mora, Silvia (författare)
Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Oresic, Matej, 1967- (författare)
Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland
Teleman, Aurelio A. (författare)
German Cancer Research Center (DKFZ), Heidelberg, Germany
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 (creator_code:org_t)
2012-01-19
2012
Engelska.
Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 8:1
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

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