Profiling metabolic remodeling in PP2Acα deficiency and chronic pressure overload mouse hearts
Open accessAbstract
Our understanding of how metabolic switches occur in the failing heart is still limited. Here, we report the emblematic pattern of metabolic alternations in two different mouse models. PP2Acα deficient hearts exhibited a dramatic decrease in the levels of mRNA encoding for transporters and enzymes involved in glucose utilization, which compensated by higher expression levels of genes controlling fatty acid utilization. These features were partly reproduced in cultured PP2Acα KD cardiomyocytes. Equivalently, a decrease in the expression of most of the transporters and enzymes controlling both glucose and fatty acid metabolism were observed in TAC model.
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Cα knockout mice had increased phospholamban Ser16 phosphorylation in the heart, while Cα transgenic mice had decreased phospholamban Ser16/Ser17 phosphorylation.
“the Cα KO mice showed increased phosphorylation of phospholamban (PLB) (Ser16) in the heart [62], while in the Cα transgenes, PLB phosphorylation (Ser16, Ser17) was found decreased [61].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [62]
In the Ppp2ca knockout, Cα expression was reduced by 80% at P11.5, while in the transgene total PP2A activity was increased 1.7-fold.
“In the KO, an 80% reduction in Cα expression was observed at P11.5 [62], while in the transgene, total PP2A activity was 1.7-fold increased [61].”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [62]
Early cardiac Cα knockout showed decreased glucose transport and glycolysis, increased aerobic glucose metabolism, and increased fatty acid transport and metabolism, suggesting a role for PP2A in regulating cardiomyocyte carbohydrate and lipid metabolism.
“In the early (at P6.5) conditional KO model of Cα in heart, evidence was obtained for decreased glucose transport and glycolysis, increased aerobic glucose metabolism, and increased fatty acid transport and metabolism [62], suggesting a role for PP2A in the regulation of carbohydrate and lipid metabolism in cardiomyocytes.”
From Physiologic functions of PP2A: Lessons from genetically modified mice (2019) · cites this paper as [62]
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Physiologic functions of PP2A: Lessons from genetically modified mice
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- Authors
- Dong, D., Li, L., Gu, P., Jin, T., Wen, M., Yuan, C., Gao, X., Liu, C., & Zhang, Z.
- Affiliations
- Nanjing Normal University (CN)
- Model Animal Research Center (CN)
- Corresponding author
- Zhang, Zhao
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2015-10-21
- Volume
- 589
- Issue
- 23
- Pages
- 3631-3639
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W1841561889
- Cited by
- 20
- References
- 42
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30871228, 31171302)
- Priority Academic Program Development of Jiangsu Higher Education Institutions (164320H106)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- metabolic remodeling, heart failure, chronic pressure overload, transverse aortic constriction, glucose metabolism, fatty acid metabolism, cardiomyocytes, metabolic switch, gene expression profiling, protein kinase A
- MeSH terms
- Adaptation, Physiological, Animals, Energy Metabolism, Heart, Hypertrophy, Male, Mice, Inbred C57BL, Cardiomyopathies, Myocardium, Organ Specificity, Pressure, Stress, Physiological, Time Factors, Mice, Protein Phosphatase 2
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