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The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms
Lipoprotein lipase (LPL) is responsible for the intravascular catabolism of triglyceride-rich lipoproteins and plays a central role in whole-body energy balance and lipid homeostasis. As such, LPL is subject to tissue-specific regulation in different physiological conditions, but the mechanisms of t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617031/ https://www.ncbi.nlm.nih.gov/pubmed/37916217 http://dx.doi.org/10.3389/fphys.2023.1271149 |
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author | Carulla, Pere Badia-Villanueva, Míriam Civit, Sergi Carrascal, Montserrat Abian, Joaquin Ricart-Jané, David Llobera, Miquel Casanovas, Albert López-Tejero, M. Dolores |
author_facet | Carulla, Pere Badia-Villanueva, Míriam Civit, Sergi Carrascal, Montserrat Abian, Joaquin Ricart-Jané, David Llobera, Miquel Casanovas, Albert López-Tejero, M. Dolores |
author_sort | Carulla, Pere |
collection | PubMed |
description | Lipoprotein lipase (LPL) is responsible for the intravascular catabolism of triglyceride-rich lipoproteins and plays a central role in whole-body energy balance and lipid homeostasis. As such, LPL is subject to tissue-specific regulation in different physiological conditions, but the mechanisms of this regulation remain incompletely characterized. Previous work revealed that LPL comprises a set of proteoforms with different isoelectric points, but their regulation and functional significance have not been studied thus far. Here we studied the distribution of LPL proteoforms in different rat tissues and their regulation under physiological conditions. First, analysis by two-dimensional electrophoresis and Western blot showed different patterns of LPL proteoforms (i.e., different pI or relative abundance of LPL proteoforms) in different rat tissues under basal conditions, which could be related to the tissue-specific regulation of the enzyme. Next, the comparison of LPL proteoforms from heart and brown adipose tissue between adults and 15-day-old rat pups, two conditions with minimal regulation of LPL in these tissues, yielded virtually the same tissue-specific patterns of LPL proteoforms. In contrast, the pronounced downregulation of LPL activity observed in white adipose tissue during fasting is accompanied by a prominent reconfiguration of the LPL proteoform pattern. Furthermore, refeeding reverts this downregulation of LPL activity and restores the pattern of LPL proteoforms in this tissue. Importantly, this reversible proteoform-specific regulation during fasting and refeeding indicates that LPL proteoforms are functionally diverse. Further investigation of potential differences in the functional properties of LPL proteoforms showed that all proteoforms exhibit lipolytic activity and have similar heparin-binding affinity, although other functional aspects remain to be investigated. Overall, this study demonstrates the ubiquity, differential distribution and specific regulation of LPL proteoforms in rat tissues and underscores the need to consider the existence of LPL proteoforms for a complete understanding of LPL regulation under physiological conditions. |
format | Online Article Text |
id | pubmed-10617031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106170312023-11-01 The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms Carulla, Pere Badia-Villanueva, Míriam Civit, Sergi Carrascal, Montserrat Abian, Joaquin Ricart-Jané, David Llobera, Miquel Casanovas, Albert López-Tejero, M. Dolores Front Physiol Physiology Lipoprotein lipase (LPL) is responsible for the intravascular catabolism of triglyceride-rich lipoproteins and plays a central role in whole-body energy balance and lipid homeostasis. As such, LPL is subject to tissue-specific regulation in different physiological conditions, but the mechanisms of this regulation remain incompletely characterized. Previous work revealed that LPL comprises a set of proteoforms with different isoelectric points, but their regulation and functional significance have not been studied thus far. Here we studied the distribution of LPL proteoforms in different rat tissues and their regulation under physiological conditions. First, analysis by two-dimensional electrophoresis and Western blot showed different patterns of LPL proteoforms (i.e., different pI or relative abundance of LPL proteoforms) in different rat tissues under basal conditions, which could be related to the tissue-specific regulation of the enzyme. Next, the comparison of LPL proteoforms from heart and brown adipose tissue between adults and 15-day-old rat pups, two conditions with minimal regulation of LPL in these tissues, yielded virtually the same tissue-specific patterns of LPL proteoforms. In contrast, the pronounced downregulation of LPL activity observed in white adipose tissue during fasting is accompanied by a prominent reconfiguration of the LPL proteoform pattern. Furthermore, refeeding reverts this downregulation of LPL activity and restores the pattern of LPL proteoforms in this tissue. Importantly, this reversible proteoform-specific regulation during fasting and refeeding indicates that LPL proteoforms are functionally diverse. Further investigation of potential differences in the functional properties of LPL proteoforms showed that all proteoforms exhibit lipolytic activity and have similar heparin-binding affinity, although other functional aspects remain to be investigated. Overall, this study demonstrates the ubiquity, differential distribution and specific regulation of LPL proteoforms in rat tissues and underscores the need to consider the existence of LPL proteoforms for a complete understanding of LPL regulation under physiological conditions. Frontiers Media S.A. 2023-10-16 /pmc/articles/PMC10617031/ /pubmed/37916217 http://dx.doi.org/10.3389/fphys.2023.1271149 Text en Copyright © 2023 Carulla, Badia-Villanueva, Civit, Carrascal, Abian, Ricart-Jané, Llobera, Casanovas and López-Tejero. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Carulla, Pere Badia-Villanueva, Míriam Civit, Sergi Carrascal, Montserrat Abian, Joaquin Ricart-Jané, David Llobera, Miquel Casanovas, Albert López-Tejero, M. Dolores The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms |
title | The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms |
title_full | The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms |
title_fullStr | The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms |
title_full_unstemmed | The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms |
title_short | The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms |
title_sort | response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617031/ https://www.ncbi.nlm.nih.gov/pubmed/37916217 http://dx.doi.org/10.3389/fphys.2023.1271149 |
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