Sex-dependent cognitive and metabolic responses to high-fat diet and exercise training in ApoB-100 transgenic mice
Brigitta Dukay1, 2, Melinda E. Tóth1, Gergő Szűcs3, Alexandra Csefová1, 2, Tamás Csont3, László Vígh1, Miklós Sántha1
1 Institute of Biochemistry, Biological Research Centre, Szeged, Hungary, 2University of Szeged, Szeged, Hungary, 3Department of Biochemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary
Increased life expectancy and sedentary lifestyle exacerbate the development of neurodegenerative disorders. A body of evidence suggest that obesity, dyslipidemia and diabetes increase the risk of dementia. On the other hand, regular physical exercise is an efficient way of preventing the consequences of aging and improving cardiometabolic health or cognitive functions. However, the exact molecular mediators of these processes are still not completely understood. Therefore, we aim to analyze the responses to regular exercise in healthy and hyperlipidemic, high-fat diet (HFD)-fed ApoB-100 overexpressing mice. The animals were subjected to daily treadmill running for 7 months. Bodyweight of the HFD-fed ApoB-100 mice increased remarkably, however, regular exercise training significantly reduced the rate of obesity. Serum cholesterol and fasting blood glucose levels increased significantly in the HFD-fed ApoB-100 mice, showing a lower level in female mice, but these were not influenced by daily exercise. The triglyceride level increased only in male ApoB-100 mice, and it was efficiently reduced by regular exercise. Regarding the locomotor activity, the total ambulatory distance and velocity were higher in the female groups in general, although regular exercise had no influence on these parameters. Using Barnes-maze, we found that regular training improved the spatial learning and memory of both ApoB-100 and wild type mice, but interestingly only in the female groups. Our results show that female mice are more active and more resistant to the HFD-induced increase in body weight, serum triglyceride and glucose levels, but more susceptible to the positive effects of regular exercise on cognitive functions. This work was supported by funding from the National Research, Development and Innovation Office, Hungary (GINOP 18.104.22.168.2016-00060, GINOP 2.3.2.-15.2016-00040) and by the ÚNKP-19-3-SZTE-67 New National Excellence Program of the Ministry for Innovation and Technology.