Maternal exercise via exerkine apelin enhances brown adipogenesis and prevents metabolic dysfunction in offspring mice

Abstract

The obesity rate is rapidly increasing, which has been attributed to lack of exercise and excessive energy intake. Here, we found a previously unidentified explanation, due to lack of maternal exercise. In this study, healthy maternal mice were assigned either to a sedentary lifestyle or to exercise daily, and fetal brown adipose tissue (BAT) development and offspring metabolic health were analyzed. Compared to the sedentary group, maternal exercise enhanced DNA demethylation of Prdm16 promoter and BAT development and prevented obesity of offspring when challenged with a high-energy diet. Apelin, an exerkine, was elevated in both maternal and fetal circulations due to exercise, and maternal administration of apelin mimicked the beneficial effects of exercise on fetal BAT development and offspring metabolic health. Together, maternal exercise enhances thermogenesis and the metabolic health of offspring mice, suggesting that the sedentary lifestyle during pregnancy contributes to the obesity epidemic in modern societies.

Maternal Inactivity Programs Skeletal Muscle Dysfunction in Offspring Mice by Attenuating Apelin Signaling and Mitochondrial Biogenesis

“…Consistently, chronic Pyrapelin 13 treatment of obese and insulin-resistant mice enhances glucose uptake and mitochondrial biogenesis in skeletal muscle ( Dray et al, 2008 ). In our previous study, we found that ME enhanced apelin levels in fetal circulation and adipose tissues of both mothers and offspring ( Son et al, 2020 ). Consistently, we observed the elevation of apelin in fetal and offspring muscle in this study, which correlated with AMPK activation and enhanced DNA demethylation in the Ppargc1a promotor.…”

Brown Adipose Tissue: New Challenges for Prevention of Childhood Obesity. A Narrative Review

“…In fact, mainly from animal models studies (as summarized in Figure 4 ), it is clear that an excessive pre-pregnancy and during pregnancy BMI, a maternal diet rich in fat and calories, together with high levels of circulating glucose and free fatty acids can promote adipogenesis in the fetus [ 26 , 27 , 28 , 29 , 30 ]. The maternal diet has an important role also during breastfeeding as if it is rich in fat it seems to reduce the thermogenic activity of BAT and the expression of UCP1 in newborn mice [ 50 ]. Instead, breastfeeding mice showed a better expression of UCP1 and may benefit from both AKGs and MFGM-PL promoting BeAT activation in iAT [ 110 ].…”

“…Although not confirmed in humans yet, this study is very interesting both because the high-fat-diet given to mice is extremely common in Western society and because it suggests that the apelin system could be a potential therapeutic target [ 50 ]. In mice, exercise during pregnancy has also been shown to act on the offspring hypothalamus and WAT inflammatory pathways, reducing the pro-inflammatory IL-6 and ameliorating glucose metabolism [ 51 ].…”

“…The idea of fetal programming is based on the so-called ‘developmental plasticity’, stating that there are specific developmental periods, such as the intra-uterine life, in which the organism adapts to environmental conditions [ 52 , 53 ]. As most studies concerning BAT modulation in response to specific environmental stimuli (as a high-fat diet, smoking or exercise) are animal studies [ 50 , 51 , 52 , 53 ], further evaluations in humans are needed, especially because BAT stimulation may be an important strategy to prevent children overweight and all the associated pathological conditions.…”

Energy Metabolism and Aging

“…It has been suggested that human BAT corresponds more closely to beige rather than brown fat in the mouse, but this is still a matter of some debate [ 57 ]. Interestingly, BAT development and metabolic health can be shaped during fetal development by maternal exercise [ 62 ].…”