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Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice
BACKGROUND: Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. METHODS: Plin5-deficient mice and Plin5/leptin-do...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478499/ https://www.ncbi.nlm.nih.gov/pubmed/37667357 http://dx.doi.org/10.1186/s13062-023-00411-8 |
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author | Jian, Lele Gao, Xing Wang, Chao Sun, Xiao Xu, Yuqiao Han, Ruili Wang, Yuying Xu, Shenhui Ding, Lan Zhou, Jingjun Gu, Yu Zhao, Yuanlin Yang, Ying Yuan, Yuan Ye, Jing Zhang, Lijun |
author_facet | Jian, Lele Gao, Xing Wang, Chao Sun, Xiao Xu, Yuqiao Han, Ruili Wang, Yuying Xu, Shenhui Ding, Lan Zhou, Jingjun Gu, Yu Zhao, Yuanlin Yang, Ying Yuan, Yuan Ye, Jing Zhang, Lijun |
author_sort | Jian, Lele |
collection | PubMed |
description | BACKGROUND: Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. METHODS: Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. RESULTS: Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. CONCLUSION: Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart. GRAPHIC ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-10478499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-104784992023-09-06 Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice Jian, Lele Gao, Xing Wang, Chao Sun, Xiao Xu, Yuqiao Han, Ruili Wang, Yuying Xu, Shenhui Ding, Lan Zhou, Jingjun Gu, Yu Zhao, Yuanlin Yang, Ying Yuan, Yuan Ye, Jing Zhang, Lijun Biol Direct Research BACKGROUND: Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. METHODS: Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. RESULTS: Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. CONCLUSION: Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart. GRAPHIC ABSTRACT: [Image: see text] BioMed Central 2023-09-04 /pmc/articles/PMC10478499/ /pubmed/37667357 http://dx.doi.org/10.1186/s13062-023-00411-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Jian, Lele Gao, Xing Wang, Chao Sun, Xiao Xu, Yuqiao Han, Ruili Wang, Yuying Xu, Shenhui Ding, Lan Zhou, Jingjun Gu, Yu Zhao, Yuanlin Yang, Ying Yuan, Yuan Ye, Jing Zhang, Lijun Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice |
title | Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice |
title_full | Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice |
title_fullStr | Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice |
title_full_unstemmed | Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice |
title_short | Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice |
title_sort | perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478499/ https://www.ncbi.nlm.nih.gov/pubmed/37667357 http://dx.doi.org/10.1186/s13062-023-00411-8 |
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