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

• Published in: Biology of sex differences 2022-01, Vol.13 (1), p.5-5, Article 5
• Main Authors: Tóth, Melinda E, Sárközy, Márta, Szűcs, Gergő, Dukay, Brigitta, Hajdu, Petra, Zvara, Ágnes, Puskás, László G, Szebeni, Gábor J, Ruppert, Zsófia, Csonka, Csaba, Kovács, Ferenc, Kriston, András, Horváth, Péter, Kővári, Bence, Cserni, Gábor, Csont, Tamás, Sántha, Miklós
• Format: Article
• Language: English
• Subjects: Adipose tissues; Age; Analysis; Analysis and chemistry; Animal models; Animals; Apolipoprotein B-100; Blood; Cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Cardiovascular system; Cellular stress response; Cholesterol; Congestive heart failure; Diet; Disease Models, Animal; Dyslipidemia; Echocardiography; Ejection fraction; Endoplasmic reticulum stress; Endurance training; Female; Females; Fibrosis; Fitness training programs; Gene expression; Genetic engineering; Glucose; Heart; Heart Failure; High density lipoprotein; High fat diet; Histology; Hypercholesterolemia; Hyperglycemia; Hyperlipidemia; Hypertension; Hypertrophy; Hypertrophy, Left Ventricular; Insulin; Insulin Resistance; Laboratory animals; Leptin; Lipids; Lipoproteins; Low density lipoprotein; Low density lipoproteins; Male; Males; Medical research; Medicine, Experimental; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - complications; Mice; Mice, Inbred C57BL; Morphology; Mortality; Obesity; Physical training; Physiological aspects; Receptors, Leptin; Risk factors; Sex; Sex differences; Sex-based differences; Stroke Volume; Transgenic animals; Type 2 diabetes; Ventricle; Weight control; Womens health
• ISSN: 2042-6410; 2042-6410
• DOI: 10.1186/s13293-022-00414-6

Metabolic 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). High-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. Both 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. HFD/APOB-100 mice showed sex-specific cardiovascular responses to MetS and ET; however, left ventricular gene expressions were similar b