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Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase

Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using...

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Autores principales: Pajed, Laura, Taschler, Ulrike, Tilp, Anna, Hofer, Peter, Kotzbeck, Petra, Kolleritsch, Stephanie, Radner, Franz P. W., Pototschnig, Isabella, Wagner, Carina, Schratter, Margarita, Eder, Sandra, Huetter, Sabrina, Schreiber, Renate, Haemmerle, Guenter, Eichmann, Thomas O., Schweiger, Martina, Hoefler, Gerald, Kershaw, Erin E., Lass, Achim, Schoiswohl, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946939/
https://www.ncbi.nlm.nih.gov/pubmed/33692445
http://dx.doi.org/10.1038/s42003-021-01858-z
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author Pajed, Laura
Taschler, Ulrike
Tilp, Anna
Hofer, Peter
Kotzbeck, Petra
Kolleritsch, Stephanie
Radner, Franz P. W.
Pototschnig, Isabella
Wagner, Carina
Schratter, Margarita
Eder, Sandra
Huetter, Sabrina
Schreiber, Renate
Haemmerle, Guenter
Eichmann, Thomas O.
Schweiger, Martina
Hoefler, Gerald
Kershaw, Erin E.
Lass, Achim
Schoiswohl, Gabriele
author_facet Pajed, Laura
Taschler, Ulrike
Tilp, Anna
Hofer, Peter
Kotzbeck, Petra
Kolleritsch, Stephanie
Radner, Franz P. W.
Pototschnig, Isabella
Wagner, Carina
Schratter, Margarita
Eder, Sandra
Huetter, Sabrina
Schreiber, Renate
Haemmerle, Guenter
Eichmann, Thomas O.
Schweiger, Martina
Hoefler, Gerald
Kershaw, Erin E.
Lass, Achim
Schoiswohl, Gabriele
author_sort Pajed, Laura
collection PubMed
description Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.
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spelling pubmed-79469392021-03-28 Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase Pajed, Laura Taschler, Ulrike Tilp, Anna Hofer, Peter Kotzbeck, Petra Kolleritsch, Stephanie Radner, Franz P. W. Pototschnig, Isabella Wagner, Carina Schratter, Margarita Eder, Sandra Huetter, Sabrina Schreiber, Renate Haemmerle, Guenter Eichmann, Thomas O. Schweiger, Martina Hoefler, Gerald Kershaw, Erin E. Lass, Achim Schoiswohl, Gabriele Commun Biol Article Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy. Nature Publishing Group UK 2021-03-10 /pmc/articles/PMC7946939/ /pubmed/33692445 http://dx.doi.org/10.1038/s42003-021-01858-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pajed, Laura
Taschler, Ulrike
Tilp, Anna
Hofer, Peter
Kotzbeck, Petra
Kolleritsch, Stephanie
Radner, Franz P. W.
Pototschnig, Isabella
Wagner, Carina
Schratter, Margarita
Eder, Sandra
Huetter, Sabrina
Schreiber, Renate
Haemmerle, Guenter
Eichmann, Thomas O.
Schweiger, Martina
Hoefler, Gerald
Kershaw, Erin E.
Lass, Achim
Schoiswohl, Gabriele
Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
title Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
title_full Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
title_fullStr Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
title_full_unstemmed Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
title_short Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
title_sort advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946939/
https://www.ncbi.nlm.nih.gov/pubmed/33692445
http://dx.doi.org/10.1038/s42003-021-01858-z
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