(588.11) Adult-Onset Exercise Improves Mitochondria Efficiency of the Heart in Female Offspring Born from Dams Fed a High-Fat and a High-Sucrose Diet

Poster Board Number: E361

Sarah Mockler (University of Texas at San Antonio), Kassandra Gonzalez (University of Texas at San Antonio), Andrea Chiñas Merlin (University of Texas at San Antonio, University of Texas at San Antonio), Yessenia Perez (University of Texas at San Antonio), U-Ter Aondo Jia (University of Texas at San Antonio), Adam Chicco (Colorado State University), Eunhee Chung (University of Texas at San Antonio)

A wealth of studies have shown that an adverse intrauterine and perinatal environment is a strong predictor for cardiometabolic diseases in offspring. Conversely, maternal exercise before and during pregnancy has been shown to diminish the risk of offspring developing metabolic disorders later in life. A few promising human and animal studies demonstrated that adult-onset exercise in offspring can overcome the detrimental effects on offspring health associated with maternal obesity. However, it is unknown whether exercise initiated by adult offspring can mitigate the negative cardiometabolic health induced by maternal obesity. Female CD-1 mice were fed either a high-fat, high-sucrose diet (HFHS) or a refined low-fat, low-sucrose diet (LFLS) for eight weeks before pregnancy and gestation, and during lactation. All dams were sedentary throughout the study. At 21 days, female offspring were weaned onto their maternal diet. At 15 weeks, offspring were randomly divided into exercise and sedentary groups which yielded 4 groups: LLS, LLE, HHS, and HHE (first letter denotes maternal diet, second letter offspring diet, and third letter indicates sedentary (S) and exercised group in offspring(E)). For exercise groups, mice had unrestricted exercise wheel access for 10 weeks. Glucose tolerance test (GTT) was performed at 25 weeks and tissues were collected to evaluate cardiac mitochondrial respiratory function at 26 weeks. Maternal diet did not affect body weight (BW) at weaning. Diet did not affect the daily average distance or hours run. BW was significantly higher in the HHS compared to other groups, but exercise did not alter final body weight. This was also true for fat mass. Exercise induced cardiac hypertrophy in mice fed LL, but not in HH mice. Surprisingly, mice in HHE had impaired glucose tolerance compared to other groups. However, no difference was found between LLE and LLS for GTT. In freshly isolated cardiac mitochondria, HHS significantly lowered the coupling efficiency of carbohydrate (pyruvate) and fatty acid (palmitoylcarnitine) oxidation compared to LLS.  Exercise training prevented these effects in the HH mice, but had no exercise effect on OXPHOS coupling with either substrate in LL mice. These results demonstrate that adult-onset exercise can prevent the deleterious effects of maternal obesity on cardiac mitochondrial function in offspring, but may alter glucose handling by mechanisms that merit further investigation.

This work was supported by the National Institute of Health [NIH, NIGMS, grant GM125603] to EC