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Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase

OBJECTIVE: Pigment epithelium–derived factor (PEDF) is an adipocyte-secreted factor involved in the development of insulin resistance in obesity. Previous studies have identified PEDF as a regulator of triacylglycerol metabolism in the liver that may act through adipose triglyceride lipase (ATGL). W...

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Autores principales: Borg, Melissa L., Andrews, Zane B., Duh, Elia J., Zechner, Rudolf, Meikle, Peter J., Watt, Matthew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292318/
https://www.ncbi.nlm.nih.gov/pubmed/21464445
http://dx.doi.org/10.2337/db10-0845
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author Borg, Melissa L.
Andrews, Zane B.
Duh, Elia J.
Zechner, Rudolf
Meikle, Peter J.
Watt, Matthew J.
author_facet Borg, Melissa L.
Andrews, Zane B.
Duh, Elia J.
Zechner, Rudolf
Meikle, Peter J.
Watt, Matthew J.
author_sort Borg, Melissa L.
collection PubMed
description OBJECTIVE: Pigment epithelium–derived factor (PEDF) is an adipocyte-secreted factor involved in the development of insulin resistance in obesity. Previous studies have identified PEDF as a regulator of triacylglycerol metabolism in the liver that may act through adipose triglyceride lipase (ATGL). We used ATGL(−/−) mice to determine the role of PEDF in regulating lipid and glucose metabolism. RESEARCH DESIGN AND METHODS: Recombinant PEDF was administered to ATGL(−/−) and wild-type mice, and whole-body energy metabolism was studied by indirect calorimetry. Adipose tissue lipolysis and skeletal muscle fatty acid metabolism was determined in isolated tissue preparations. Muscle lipids were assessed by electrospray ionization–tandem mass spectrometry. Whole-body insulin sensitivity and skeletal muscle glucose uptake were assessed. RESULTS: PEDF impaired the capacity to adjust substrate selection, resulting in a delayed diurnal decline in the respiratory exchange ratio, and suppressed daily fatty acid oxidation. PEDF enhanced adipocyte lipolysis and triacylglycerol lipase activity in skeletal muscle. Muscle fatty acid uptake and storage were unaffected, whereas fatty acid oxidation was impaired. These changes in lipid metabolism were abrogated in ATGL(−/−) mice and were not attributable to hypothalamic actions. ATGL(−/−) mice were also refractory to PEDF-mediated insulin resistance, but this was not related to changes in lipid species in skeletal muscle. CONCLUSIONS: The results are the first direct demonstration that 1) PEDF influences systemic fatty acid metabolism by promoting lipolysis in an ATGL-dependent manner and reducing fatty acid oxidation and 2) ATGL is required for the negative effects of PEDF on insulin action.
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spelling pubmed-32923182012-05-01 Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase Borg, Melissa L. Andrews, Zane B. Duh, Elia J. Zechner, Rudolf Meikle, Peter J. Watt, Matthew J. Diabetes Metabolism OBJECTIVE: Pigment epithelium–derived factor (PEDF) is an adipocyte-secreted factor involved in the development of insulin resistance in obesity. Previous studies have identified PEDF as a regulator of triacylglycerol metabolism in the liver that may act through adipose triglyceride lipase (ATGL). We used ATGL(−/−) mice to determine the role of PEDF in regulating lipid and glucose metabolism. RESEARCH DESIGN AND METHODS: Recombinant PEDF was administered to ATGL(−/−) and wild-type mice, and whole-body energy metabolism was studied by indirect calorimetry. Adipose tissue lipolysis and skeletal muscle fatty acid metabolism was determined in isolated tissue preparations. Muscle lipids were assessed by electrospray ionization–tandem mass spectrometry. Whole-body insulin sensitivity and skeletal muscle glucose uptake were assessed. RESULTS: PEDF impaired the capacity to adjust substrate selection, resulting in a delayed diurnal decline in the respiratory exchange ratio, and suppressed daily fatty acid oxidation. PEDF enhanced adipocyte lipolysis and triacylglycerol lipase activity in skeletal muscle. Muscle fatty acid uptake and storage were unaffected, whereas fatty acid oxidation was impaired. These changes in lipid metabolism were abrogated in ATGL(−/−) mice and were not attributable to hypothalamic actions. ATGL(−/−) mice were also refractory to PEDF-mediated insulin resistance, but this was not related to changes in lipid species in skeletal muscle. CONCLUSIONS: The results are the first direct demonstration that 1) PEDF influences systemic fatty acid metabolism by promoting lipolysis in an ATGL-dependent manner and reducing fatty acid oxidation and 2) ATGL is required for the negative effects of PEDF on insulin action. American Diabetes Association 2011-05 2011-04-23 /pmc/articles/PMC3292318/ /pubmed/21464445 http://dx.doi.org/10.2337/db10-0845 Text en © 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Metabolism
Borg, Melissa L.
Andrews, Zane B.
Duh, Elia J.
Zechner, Rudolf
Meikle, Peter J.
Watt, Matthew J.
Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
title Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
title_full Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
title_fullStr Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
title_full_unstemmed Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
title_short Pigment Epithelium–Derived Factor Regulates Lipid Metabolism via Adipose Triglyceride Lipase
title_sort pigment epithelium–derived factor regulates lipid metabolism via adipose triglyceride lipase
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292318/
https://www.ncbi.nlm.nih.gov/pubmed/21464445
http://dx.doi.org/10.2337/db10-0845
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