EXERCISE-INDUCED HORMONE, APELIN, IN MEDIATING FETAL MUSCLE AND ADIPOSE DEVELOPMENT

Junseok Son

Obesity is a worsening problem and rapidly increasing in the U.S. and worldwide. Notably, accumulating studies have shown an inherent link between maternal obesity (MO) and metabolic dysfunction in children. Recently, several studies demonstrated that maternal exercise (ME) enhances the capacity of offspring to maintain metabolic homeostasis, which might protect metabolic disorders in the offspring due to MO. The underlying mechanisms, on the other hand, remain to be defined. The placenta is the key tissue mediating nutrients and oxygen delivery to fetuses and its development during pregnancy is impeded due to MO. We hypothesized that ME improves maternal metabolic health and prevents fetal overgrowth induced by maternal high fat diet (HFD)-induced obesity. First, we discovered that placental vascularization/angiogenesis and nutrient transport activities were impaired by MO, which was protected by exercise during pregnancy. Interestingly, in the placenta, a hormone, apelin, known to stimulate angiogenesis, was highly activated in response to exercise, but down-regulated by MO. Consistently, circulating apelin levels in both mothers and fetuses were elevated due to ME. To further explore roles of apelin, we studied whether ME stimulates brown and beige adipose tissue development and enhances their thermogenic activity in the offspring, showing that maternal administration of apelin mimicked the beneficial effects of exercise on offspring metabolic health through stimulating brown/beige adipogenesis, which could suggest a novel therapeutic approach for protecting programming effect of maternal inactivity on offspring obesity. Besides, since brown fat and muscle are major tissues responsible for metabolic homeostasis, we additionally studied the effect of ME on fetal and offspring muscle development, showing that ME enhanced mitochondrial biogenesis in fetal and offspring skeletal muscle, which enhances exercise endurance capacity and metabolic health of the offspring muscle. In summary, exercise-induced apelin is a feasible target to promote brown fat and muscle development, which positively affects not only mothers themselves, but their offspring.

EXERCISE-INDUCED HORMONE, APELIN, IN MEDIATING FETAL MUSCLE AND ADIPOSE DEVELOPMENT

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