부산대학교 도서관

Introduction:Experimental data have shown that maternal obesity can lead to metabolic impairment and cardiovascular diseases on the next generation later in life. Our model showed a cardiac dysfunction without any metabolic changes, offering a better understanding of the development of the cardiac disease itself.Methods:4-week old C57BL/6J females were fed control (6% fat; NC) or high-fat diet (45% or 60% fat; HF45 and HF60) ad libitumfor six weeks (F0). To characterize the model, F0 was phenotyped for body composition (NMR) and glucose tolerance (GTT) before breeding, at ten weeks of age. F0 NC, HF45, and HF60 females were mated with NC males to produce F1 offspring (F1). To increase the maternal diet influence, F1 mice were intercrossed within their group to obtain the F2 generation (F2). Except for F0 animals, all mice were kept on a control diet throughout the experiment. NMR, GTT and echocardiogram were performed on F1 and F2 at 25 weeks of age.Results:F0-HF45 and HF60 mice displayed higher body weight and fat mass, but only HF60 females had a glucose handling impairment. No changes were observed among groups regarding pregnancy rate and litter size at birth, but the HF60 females had a decrease in pup survival rate after weaning. Regarding the offspring, only F1-HF45 males exhibited increased body weight and fat mass. F1-HF45 and F1-HF60 males had a glucose impairment, noted by an increased AUC. Interestingly, F2-HF45 males displayed a decrease in body weight with a trending reduced fat mass, characterizing a paradox effect of maternal obesity on the subsequent generation?s body weight. Normal cardiac function was detected in F1-HF45 and F1-HF60 males, but a substantial reduction on ejection fraction and increased left ventricle end-systolic volume was observed in F2-HF45.Conclusions:Our results demonstrate that: (1) the amount of maternal fat consumption can lead to a smaller litter size after weaning, and (2) the intergenerational transmission of cardiac dysfunction through maternal obesity in mice is independent of obesity transmission, even skipping one generation.