Exercise training worsens cardiac performance in males but does not change ejection fraction and improves hypertrophy in females in a mouse model of metabolic syndrome

Biology of Sex Differences

Research

Gábor Cserni¹  Bence Kővári¹  Melinda E. Tóth²  Brigitta Dukay²  Petra Hajdu²  Miklós Sántha²  Zsófia Ruppert³  Gábor J. Szebeni⁴  László G. Puskás⁴  Ágnes Zvara⁴  Márta Sárközy⁵  Gergő Szűcs⁵  Tamás Csont⁵  Csaba Csonka⁵  András Kriston⁶  Ferenc Kovács⁶  Péter Horváth⁷ 

[1] Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Állomás utca 1, 6720, Szeged, Hungary;Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, 6726, Szeged, Hungary;Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, 6726, Szeged, Hungary;Doctoral School in Biology, University of Szeged, Szeged, Hungary;Laboratory of Functional Genomics, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, 6726, Szeged, Hungary;MEDICS Research Group, Department of Biochemistry, University of Szeged Albert Szent-Györgyi Medical School, Dóm tér 9, 6720, Szeged, Hungary;Interdisciplinary Center of Excellence, University of Szeged, Dugonics tér 13, 6720, Szeged, Hungary;Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, 6726, Szeged, Hungary;Single-Cell Technologies Ltd, Temesvári krt. 62, 6726, Szeged, Hungary;Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, 6726, Szeged, Hungary;Single-Cell Technologies Ltd, Temesvári krt. 62, 6726, Szeged, Hungary;Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00014, Helsinki, Finland;

关键词: Metabolic syndrome;    Hyperlipidemia;    Obesity;    Endoplasmic reticulum stress;    Sex-based differences;    Endurance training;    Cardio-metabolic disease;    Heart failure;    Left ventricular hypertrophy;    Diastolic function;   

DOI  :  10.1186/s13293-022-00414-6

 received in 2021-09-16, accepted in 2022-01-05,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundMetabolic syndrome (MetS) refers to a cluster of co-existing cardio-metabolic risk factors, including visceral obesity, dyslipidemia, hyperglycemia with insulin resistance, and hypertension. As there is a close link between MetS and cardiovascular diseases, we aimed to investigate the sex-based differences in MetS-associated heart failure (HF) and cardiovascular response to regular exercise training (ET).MethodsHigh-fat diet-fed male and female APOB-100 transgenic (HFD/APOB-100, 3 months) mice were used as MetS models, and age- and sex-matched C57BL/6 wild-type mice on standard diet served as healthy controls (SD/WT). Both the SD/WT and HFD/APOB-100 mice were divided into sedentary and ET groups, the latter running on a treadmill (0.9 km/h) for 45 min 5 times per week for 7 months. At month 9, transthoracic echocardiography was performed to monitor cardiac function and morphology. At the termination of the experiment at month 10, blood was collected for serum low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol measurements and homeostatic assessment model for insulin resistance (HOMA-IR) calculation. Cardiomyocyte hypertrophy and fibrosis were assessed by histology. Left ventricular expressions of selected genes associated with metabolism, inflammation, and stress response were investigated by qPCR.ResultsBoth HFD/APOB-100 males and females developed obesity and hypercholesterolemia; however, only males showed insulin resistance. ET did not change these metabolic parameters. HFD/APOB-100 males showed echocardiographic signs of mild HF with dilated ventricles and thinner walls, whereas females presented the beginning of left ventricular hypertrophy. In response to ET, SD/WT males developed increased left ventricular volumes, whereas females responded with physiologic hypertrophy. Exercise-trained HFD/APOB-100 males presented worsening HF with reduced ejection fraction; however, ET did not change the ejection fraction and reversed the echocardiographic signs of left ventricular hypertrophy in HFD/APOB-100 females. The left ventricular expression of the leptin receptor was higher in females than males in the SD/WT groups. Left ventricular expression levels of stress response-related genes were higher in the exercise-trained HFD/APOB-100 males and exercise-trained SD/WT females than exercise-trained SD/WT males.ConclusionsHFD/APOB-100 mice showed sex-specific cardiovascular responses to MetS and ET; however, left ventricular gene expressions were similar between the groups except for leptin receptor and several stress response-related genes.

【 授权许可】

CC BY   
© The Author(s) 2022. corrected publication 2023

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