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Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: a two-hit model of hypertrophic cardiomyopathy

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Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: a two-hit model of hypertrophic cardiomyopathy. / Nollet, Edgar E.; Algül, Sila; Goebel, Max; Schlossarek, Saskia; van der Wel, Nicole N.; Jans, Judith J. M.; van de Wiel, Mark A.; Knol, Jaco C.; Pham, Thang C.; Piersma, Sander R.; de Goeij-de Haas, Richard; Hermans, Jill; van Klinken, Jan Bert; van Weeghel, Michel; Houtkooper, Riekelt H.; Carrier, Lucie; Jimenez, Connie R.; Kuster, Diederik W. D.; van der Velden, Jolanda.

in: Journal of molecular and cellular cardiology plus, Jahrgang 6, 100050, 19.11.2023.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Nollet, EE, Algül, S, Goebel, M, Schlossarek, S, van der Wel, NN, Jans, JJM, van de Wiel, MA, Knol, JC, Pham, TC, Piersma, SR, de Goeij-de Haas, R, Hermans, J, van Klinken, JB, van Weeghel, M, Houtkooper, RH, Carrier, L, Jimenez, CR, Kuster, DWD & van der Velden, J 2023, 'Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: a two-hit model of hypertrophic cardiomyopathy', Journal of molecular and cellular cardiology plus, Jg. 6, 100050. https://doi.org/10.1016/j.jmccpl.2023.100050

APA

Nollet, E. E., Algül, S., Goebel, M., Schlossarek, S., van der Wel, N. N., Jans, J. J. M., van de Wiel, M. A., Knol, J. C., Pham, T. C., Piersma, S. R., de Goeij-de Haas, R., Hermans, J., van Klinken, J. B., van Weeghel, M., Houtkooper, R. H., Carrier, L., Jimenez, C. R., Kuster, D. W. D., & van der Velden, J. (2023). Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: a two-hit model of hypertrophic cardiomyopathy. Journal of molecular and cellular cardiology plus, 6, [100050]. https://doi.org/10.1016/j.jmccpl.2023.100050

Vancouver

Nollet EE, Algül S, Goebel M, Schlossarek S, van der Wel NN, Jans JJM et al. Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: a two-hit model of hypertrophic cardiomyopathy. Journal of molecular and cellular cardiology plus. 2023 Nov 19;6. 100050. https://doi.org/10.1016/j.jmccpl.2023.100050

Bibtex

@article{e2028d8ba8734a83bb115066fe7e70b3,
title = "Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: a two-hit model of hypertrophic cardiomyopathy",
abstract = "Background and aim: Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy and dysfunction in heterozygous (HET) Mybpc3c.772G>A knock-in mice.Methods and results: Wild-type (WT) and HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks. Metabolomic analyses on serum revealed systemic metabolic derailment in WD-fed WT and HET mice. Strikingly, only WD-fed HET mice developed cardiac hypertrophy and dysfunction, which was not driven by aggravated cardiac myosin binding protein-C haploinsufficiency. WD reduced oxidative phosphorylation and increased toxic lipids in the heart irrespective of genotype. Cardiac proteomic analyses revealed higher abundanceof proteins involved in fatty acid oxidation in WD-fed mice, however this increase was blunted in HET compared to WT mice. Accordingly, cardiac metabolomic and lipidomic analyses showed accumulation of acylcarnitines in WD-fed HET vs WT mice.Conclusion: WD feeding triggered cardiac dysfunction and hypertrophy in otherwise phenotype-negative HET Mybpc3c.772G>A mice. We propose that the presence of a HCM mutation predisposes the heart to metabolic inflexibility when subjected to systemic metabolic stress. Our study represents a novel approach to study the interplay between unfavorable metabolic health and mutation-induced defects in HCM disease development.",
author = "Nollet, {Edgar E.} and Sila Alg{\"u}l and Max Goebel and Saskia Schlossarek and {van der Wel}, {Nicole N.} and Jans, {Judith J. M.} and {van de Wiel}, {Mark A.} and Knol, {Jaco C.} and Pham, {Thang C.} and Piersma, {Sander R.} and {de Goeij-de Haas}, Richard and Jill Hermans and {van Klinken}, {Jan Bert} and {van Weeghel}, Michel and Houtkooper, {Riekelt H.} and Lucie Carrier and Jimenez, {Connie R.} and Kuster, {Diederik W. D.} and {van der Velden}, Jolanda",
year = "2023",
month = nov,
day = "19",
doi = "10.1016/j.jmccpl.2023.100050",
language = "English",
volume = "6",
journal = "Journal of molecular and cellular cardiology plus",
issn = "2772-9761",

}

RIS

TY - JOUR

T1 - Western diet triggers cardiac dysfunction in heterozygous Mybpc3-targeted knock-in mice: a two-hit model of hypertrophic cardiomyopathy

AU - Nollet, Edgar E.

AU - Algül, Sila

AU - Goebel, Max

AU - Schlossarek, Saskia

AU - van der Wel, Nicole N.

AU - Jans, Judith J. M.

AU - van de Wiel, Mark A.

AU - Knol, Jaco C.

AU - Pham, Thang C.

AU - Piersma, Sander R.

AU - de Goeij-de Haas, Richard

AU - Hermans, Jill

AU - van Klinken, Jan Bert

AU - van Weeghel, Michel

AU - Houtkooper, Riekelt H.

AU - Carrier, Lucie

AU - Jimenez, Connie R.

AU - Kuster, Diederik W. D.

AU - van der Velden, Jolanda

PY - 2023/11/19

Y1 - 2023/11/19

N2 - Background and aim: Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy and dysfunction in heterozygous (HET) Mybpc3c.772G>A knock-in mice.Methods and results: Wild-type (WT) and HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks. Metabolomic analyses on serum revealed systemic metabolic derailment in WD-fed WT and HET mice. Strikingly, only WD-fed HET mice developed cardiac hypertrophy and dysfunction, which was not driven by aggravated cardiac myosin binding protein-C haploinsufficiency. WD reduced oxidative phosphorylation and increased toxic lipids in the heart irrespective of genotype. Cardiac proteomic analyses revealed higher abundanceof proteins involved in fatty acid oxidation in WD-fed mice, however this increase was blunted in HET compared to WT mice. Accordingly, cardiac metabolomic and lipidomic analyses showed accumulation of acylcarnitines in WD-fed HET vs WT mice.Conclusion: WD feeding triggered cardiac dysfunction and hypertrophy in otherwise phenotype-negative HET Mybpc3c.772G>A mice. We propose that the presence of a HCM mutation predisposes the heart to metabolic inflexibility when subjected to systemic metabolic stress. Our study represents a novel approach to study the interplay between unfavorable metabolic health and mutation-induced defects in HCM disease development.

AB - Background and aim: Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy and dysfunction in heterozygous (HET) Mybpc3c.772G>A knock-in mice.Methods and results: Wild-type (WT) and HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks. Metabolomic analyses on serum revealed systemic metabolic derailment in WD-fed WT and HET mice. Strikingly, only WD-fed HET mice developed cardiac hypertrophy and dysfunction, which was not driven by aggravated cardiac myosin binding protein-C haploinsufficiency. WD reduced oxidative phosphorylation and increased toxic lipids in the heart irrespective of genotype. Cardiac proteomic analyses revealed higher abundanceof proteins involved in fatty acid oxidation in WD-fed mice, however this increase was blunted in HET compared to WT mice. Accordingly, cardiac metabolomic and lipidomic analyses showed accumulation of acylcarnitines in WD-fed HET vs WT mice.Conclusion: WD feeding triggered cardiac dysfunction and hypertrophy in otherwise phenotype-negative HET Mybpc3c.772G>A mice. We propose that the presence of a HCM mutation predisposes the heart to metabolic inflexibility when subjected to systemic metabolic stress. Our study represents a novel approach to study the interplay between unfavorable metabolic health and mutation-induced defects in HCM disease development.

UR - https://www.sciencedirect.com/science/article/pii/S277297612300020X

U2 - 10.1016/j.jmccpl.2023.100050

DO - 10.1016/j.jmccpl.2023.100050

M3 - SCORING: Journal article

VL - 6

JO - Journal of molecular and cellular cardiology plus

JF - Journal of molecular and cellular cardiology plus

SN - 2772-9761

M1 - 100050

ER -