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Title: | Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
Author: | Guitart de la Rosa, Maria Osorio Conles, Óscar Pentinat Pelegrin, Thais Cebrià, Judith García Villoria, Judit Sala Cano, David Sebastián Muñoz, David Zorzano Olarte, Antonio Ribes Rubió, Maria Antònia Jiménez Chillarón, José Carlos García Martínez, Celia Gómez Foix, Anna Maria |
Keywords: | Aparell locomotor Metabolisme energètic Glicogen Àcids grassos Diabetis Proteïnes de membrana Mitocondris Musculoskeletal system Energy metabolism Glycogen Fatty acids Diabetes Membrane proteins Mitochondria |
Issue Date: | 23-May-2014 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | FATP1 mediates skeletal muscle cell fatty acid import, yet its intracellular localization and metabolic control role are not completely defined. Here, we examine FATP1 localization and metabolic effects of its overexpression in mouse skeletal muscle. The FATP1 protein was detected in mitochondrial and plasma membrane fractions, obtained by differential centrifugation, of mouse gastrocnemius muscle. FATP1 was most abundant in purified mitochondria, and in the outer membrane and soluble intermembrane, but not in the inner membrane plus matrix, enriched subfractions of purified mitochondria. Immunogold electron microscopy localized FATP1-GFP in mitochondria of transfected C2C12 myotubes. FATP1 was overexpressed in gastrocnemius mouse muscle, by adenovirus-mediated delivery of the gene into hindlimb muscles of newborn mice, fed after weaning a chow or high-fat diet. Compared to GFP delivery, FATP1 did not alter body weight, serum fed glucose, insulin and triglyceride levels, and whole-body glucose tolerance, in either diet. However, fatty acid levels were lower and beta-hydroxybutyrate levels were higher in FATP1-than GFP-mice, irrespective of diet. Moreover, intramuscular triglyceride content was lower in FATP1-versus GFP-mice regardless of diet, and beta-hydroxybutyrate content was unchanged in high-fat-fed mice. Electroporation-mediated FATP1 overexpression enhanced palmitate oxidation to CO2, but not to acid-soluble intermediate metabolites, while CO2 production from beta-hydroxybutyrate was inhibited and that from glucose unchanged, in isolated mouse gastrocnemius strips. In summary, FATP1 was localized in mitochondria, in the outer membrane and intermembrane parts, of mouse skeletal muscle, what may be crucial for its metabolic effects. Overexpressed FATP1 enhanced disposal of both systemic fatty acids and intramuscular triglycerides. Consistently, it did not contribute to the high-fat diet-induced metabolic dysregulation. However, FATP1 lead to hyperketonemia, likely secondary to the sparing of ketone body oxidation by the enhanced oxidation of fatty acids. |
Note: | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0098109 |
It is part of: | PLoS One, 2014, vol. 9, num. 5, p. e98109 |
URI: | http://hdl.handle.net/2445/59231 |
Related resource: | http://dx.doi.org/10.1371/journal.pone.0098109 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
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