The novel myokine irisin has been reported as a therapeutic target for metabolic disease. The objective of this study is to reveal the effects of aerobic training (AT) and resistance training (RT) on circulating irisin levels and their associations with change of body composition in overweight/obese adults. Twenty eight overweight/obese adults (BMI>23 kg/m2) were included in this study and compared before and after 8 weeks of exercise program (60 min/day, 5 times in a week). The subjects, in both aerobic and resistance training, showed significant improvement in anthropometric parameters and exercise capacities including maximal oxygen uptake and muscle strength. Interestingly, the circulating irisin was significantly increased in resistance training group (p=0.002) but not in aerobic training (p=0.426) compared to control group. In addition, we found the positive correlation between change of the circulating irisin and muscle mass (r=0.432, p=0.022) and the negative correlation between change of the circulating irisin and fat mass (r=−0.407, p=0.031). In the present pilot study, we found that circulating irisin level was increased by 8 weeks of resistance training in overweight/obese adults, suggesting that resistance training could be the efficient exercise type in overweight/obese considering positive change of body composition concomitant with increase of irisin levels.

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.

Key points: Maternal exercise improves the metabolic health of maternal mice challenged with a high‐fat diet. Exercise intervention of obese mothers prevents fetal overgrowth. Exercise intervention reverses impaired placental vascularization in obese mice. Maternal exercise activates placental AMP‐activated protein kinase, which was inhibited as a result of maternal obesity. More than one‐third of pregnant women in the USA are obese and maternal obesity (MO) negatively affects fetal development, which predisposes offspring to metabolic diseases. The placenta mediates nutrient delivery to fetuses and its function is impaired as a result of MO. Exercise ameliorates metabolic dysfunction resulting from obesity, although its effect on placental function of obese mothers has not been explored. In the present study, C57BL/6J female mice were randomly assigned into two groups fed either a control or a high‐fat diet (HFD) and then the mice on each diet were further divided into two subgroups with/without exercise. In HFD‐induced obese mice, daily treadmill exercise during pregnancy reduced body weight gain, lowered serum glucose and lipid concentration, and improved insulin sensitivity of maternal mice. Importantly, maternal exercise prevented fetal overgrowth (macrosomia) induced by MO. To further examine the preventive effects of exercise on fetal overgrowth, placental vascularization and nutrient transporters were analysed. Vascular density and the expression of vasculogenic factors were reduced as a result of MO but were recovered by maternal exercise. On the other hand, the contents of nutrient transporters were not substantially altered by MO or exercise, suggesting that the protective effects of exercise in MO‐induced fetal overgrowth were primarily a result of the alteration of placental vascularization and improved maternal metabolism. Furthermore, exercise enhanced downstream insulin signalling and activated AMP‐activated protein kinase in HFD placenta. In sum, maternal exercise prevented fetal overgrowth induced by MO, which was associated with improved maternal metabolism and placental vascularization in obese mothers with exercise.

During muscle regeneration, excessive formation of adipogenic and fibrogenic tissues, from their respective fibro/adipogenic progenitors (FAPs), impairs functional recovery. Intrinsic mechanisms controlling the proliferation and differentiation of FAPs remain largely unexplored. Here, we investigated the role of retinoic acid (RA) signalling in regulating FAPs and the subsequent effects on muscle restoration from a cardiotoxin-induced injury. Blockage of retinoic acid receptor (RAR) signalling was achieved through dominant negative retinoic acid receptor α (RARα403) expression specific in PDGFRα+ FAPs in vivo and by BMS493 treatment in vitro. Effects of RAR-signalling on FAP cellularity and muscle regeneration were also investigated in a high-fat diet-induced obese mice model. Supplementation of RA increased the proliferation of FAPs during the early stages of regeneration while suppressing FAP differentiation and promoting apoptosis during the remodelling stage. Loss of RAR-signalling caused ectopic adipogenic differentiation of FAPs and impaired muscle regeneration. Furthermore, obesity disrupted the cellular transition of FAPs and attenuated muscle regeneration. Supplementation of RA to obese mice not only rescued impaired muscle fibre regeneration, but also inhibited infiltration of fat and fibrotic tissues during muscle repair. These beneficial effects were abolished after blocking RAR-signalling in FAPs of obese mice. These data suggest that RAR-signalling in FAPs is a critical therapeutic target for suppressing differentiation of FAPs and facilitating the regeneration of muscle and other tissues. This study was supported by grants from the National Institutes of Health (R01-HD067449 and R21-AG049976) to M.D.

Although maternal exercise (ME) becomes increasingly uncommon, the effects of ME on offspring muscle metabolic health remain largely undefined. Maternal mice are subject to daily exercise during pregnancy, which enhances mitochondrial biogenesis during fetal muscle development; this is correlated with higher mitochondrial content and oxidative muscle fibers in offspring muscle and improved endurance capacity. Apelin, an exerkine, is elevated due to ME, and maternal apelin administration mirrors the effect of ME on mitochondrial biogenesis in fetal muscle. Importantly, both ME and apelin induce DNA demethylation of the peroxisome proliferator-activated receptor γ coactivator-1α (Ppargc1a) promoter and enhance its expression and mitochondrial biogenesis in fetal muscle. Such changes in DNA methylation were maintained in offspring, with ME offspring muscle expressing higher levels of PGC-1α1/4 isoforms, explaining improved muscle function. In summary, ME enhances DNA demethylation of the Ppargc1a promoter in fetal muscle, which has positive programming effects on the exercise endurance capacity and protects offspring muscle against metabolic dysfunction.

Maternal obesity (MO) and gestational diabetes mellitus (GDM) are common in Western societies, which impair fetal development and predispose offspring to metabolic dysfunction. Placenta is the organ linking the mother to her fetus, and MO suppresses the development of vascular system and expression of nutrient transporters in placenta, thereby affecting fetal development. For maintaining its proper physiological function, placenta is energy demanding, which is met through extensive oxidative phosphorylation. However, the oxidative capacity of placenta is suppressed due to MO and GDM. Recently, several studies showed that physical activity during pregnancy enhances oxidative metabolism and improves placental function, which might be partially mediated by exerkines, referring to cytokines elicited by exercise. In addition, as an endocrine organ, placenta secretes cytokines, termed placentokines, including apelin, superoxide dismutase 3, irisin, and adiponectin, which mediate fetal development and maternal metabolism. Possible molecular mechanisms linking maternal exercise and placentokines to placental and fetal development are further discussed. As an emerging field, up to now, available studies are limited, mostly conducted in rodents. Given the epidemics of obesity and metabolic disorders, as well as the prevalence of maternal sedentary lifestyle, the effects of exercise of pregnant women on placental function and placentokine secretion, as well as their impacts on fetal development, need to be further examined.