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Abstract Background Following muscle injury, fibro‐adipogenic progenitors (FAPs) are rapidly activated and undergo apoptosis at the resolution stage, which is required for proper muscle regeneration. When excessive FAPs remain, it contributes to fibrotic and fatty infiltration, impairing muscle recovery. Mechanisms controlling FAP apoptosis remain poorly defined. We hypothesized that AMP‐activated protein kinase (AMPK) in FAPs mediates their apoptosis during the muscle regeneration. Methods To test, AMPKα1fl/fl PDGFRαCre mice were used to knock out AMPKα1 in FAPs. Following AMPKα1 knockout, the mice were injected with phosphate‐buffered saline or glycerol to induce muscle injury. Tibialis anterior muscle and FAPs were collected at 3, 7 and 14 days post‐injury (dpi) for further analysis. Results We found that AMPKα1 deletion in FAPs enhanced p65 translocation to the nuclei by 110% (n = 3; P

Abstract Over the past few decades, genetic selection and refined nutritional management have extensively been used to increase the growth rate and lean meat production of livestock. However, the rapid growth rates of modern breeds are often accompanied by a reduction in intramuscular fat deposition and increased occurrences of muscle abnormalities, impairing meat quality and processing functionality. Early stages of animal development set the long-term growth trajectory of offspring. However, due to the seasonal reproductive cycles of ruminant livestock, gestational nutrient deficiencies caused by seasonal variations, frequent droughts, and unfavorable geological locations negatively affect fetal development and their subsequent production efficiency and meat quality. Therefore, enrolling livestock in nutritional intervention strategies during gestation is effective for improving the body composition and meat quality of the offspring at harvest. These crucial early developmental stages include embryonic, fetal, and postnatal stages, which have stage-specific effects on subsequent offspring development, body composition, and meat quality. This review summarizes contemporary research in the embryonic, fetal, and neonatal development, and the impacts of maternal nutrition on the early development and programming effects on the long-term growth performance of livestock. Understanding the developmental and metabolic characteristics of skeletal muscle, adipose, and fibrotic tissues will facilitate the development of stage-specific nutritional management strategies to optimize production efficiency and meat quality.

Endothelial mitochondria play a pivotal role in maintaining endothelial cell (EC) homeostasis through constantly altering their size, shape, and intracellular localization. Studies show that the disruption of the basal mitochondrial network in EC, forming excess fragmented mitochondria, implicates cardiovascular disease. However, cellular consequences underlying the morphological changes in the endothelial mitochondria under distinctively different, but physiologically occurring, flow patterns (i.e., unidirectional flow [UF] versus disturbed flow [DF]) are largely unknown. The purpose of this study was to investigate the effect of different flow patterns on mitochondrial morphology and its implications in EC phenotypes. We show that mitochondrial fragmentation is increased at DF-exposed vessel regions, where elongated mitochondria are predominant in the endothelium of UF-exposed regions. DF increased dynamin-related protein 1 (Drp1), mitochondrial reactive oxygen species (mtROS), hypoxia-inducible factor 1, glycolysis, and EC activation. Inhibition of Drp1 significantly attenuated these phenotypes. Carotid artery ligation and microfluidics experiments further validate that the significant induction of mitochondrial fragmentation was associated with EC activation in a Drp1-dependent manner. Contrarily, UF in vitro or voluntary exercise in vivo significantly decreased mitochondrial fragmentation and enhanced fatty acid uptake and OXPHOS. Our data suggest that flow patterns profoundly change mitochondrial fusion/fission events, and this change contributes to the determination of proinflammatory and metabolic states of ECs.

Summary: Background: Sarcolipin and uncoupling protein 3 (UCP3) mediate muscle-based non-shivering thermogenesis (NST) to improve metabolic homeostasis. The impacts of maternal obesity (MO) and maternal exercise (ME) on NST in offspring muscle remain unexamined. Methods: Female mice were fed with a control diet or high fat diet to induce obesity. Then, obese mice were further separated into two groups: obesity only (OB) and OB plus daily exercise (OB/Ex). Fetal muscle was collected at embryonic day 18.5 and offspring mice at 3-month-old. Apelin administration during pregnancy and apelin receptor (APJ) knockout mouse were further used for investigating the mediatory role of APJ on muscle-based thermogenesis. To explore the direct effects of exercise on AMP-activated protein kinase (AMPK) downstream targets, AMPK knockout mouse was used. Findings: MO inhibited while ME activated AMPK and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in fetal muscle. AMPK activation increased sarcolipin expression, which inhibited the uptake of calcium ions into sarcoplasmic reticulum, thereby activating CaMKK2. Consistently, the expression of UCP3 and sarcolipin was suppressed due to MO but activated in ME fetal muscle. Importantly, changes of UCP3 and sarcolipin maintained in offspring muscle, showing the transgenerational effects. Furthermore, apelin administration during pregnancy mimicked the effects of ME on AMPK and CaMKK2 activation, and UCP3 and sarcolipin expression, underscoring the mediatory roles of apelin-AMPK signaling in improving fetal muscle development. Interpretation: ME, via activation of apelin signaling-AMPK axis, enhances NST gene expression in fetal and offspring muscle impaired due to MO, which intergenerationally protects offspring from diet-induced obesity and metabolic disorders. Funding: This work was supported by National Institutes of Health Grant R01-HD067449.

Summary: 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.

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: This study was supported by grants from the National Institutes of Health (R01-HD067449 and R21-AG049976) to M.D.

Abstract Background Since the 1980s, restructuring, which includes downsizing, closures, mergers, and privatization, has expanded worldwide, and various studies have investigated its effect on health. However, previous studies have mainly focused on restructuring accompanied by massive lay-offs, and the effect of a merger on workers’ health is still controversial. This study aims to investigate changes in worker depression and job stress after a merger without downsizing, which is unusual in Korea. Methods Repeated surveys were done in April 2014, April 2015, and April 2016 involving the participation of 209 subjects. Participants were divided into two groups, which were comprised of blue-collar workers (104) and white-collar workers (105). Sociodemographic characteristics, including age, education level, job tenure, gender, marital status, smoking status, and alcohol consumption, were measured via a survey. To determine the level of depression, the Korean version of the Center for Epidemiologic Studies Depression Scale (CES-D) was employed, and to investigate job stress, the Korean Occupational Stress Scale-Short Form (KOSS-SF) was used. For statistical analyses, Pearson’s chi-square test, the Student’s t-test, and repeated measure analysis of variance (ANOVA) were performed. Results The results showed that depression (CES-D, F[2, 400] = 0.466, p = 0.628) was changed but without significance and job stress (KOSS-SF, F[1.899, 379.831] = 3.192, p = 0.045) were significantly different. The between-group difference in the CES-D score between the blue- and white-collar workers by survey administration time was not statistically significant (F = 0.316, p = 0.574). The interaction between the survey time and occupational group was also not statistically significant (F = 0.967, p = 0.381). The between-group difference in the KOSS-SF total score was not statistically significant (F = 1.132, p = 0.289), and the interaction between the survey administration time and occupational group was also not significant (F = 0.817, p = 0.437). In the job stress subgroup analyses Job insecurity and Lack of reward showed a significant difference by survey administration time. Conclusion This study showed that a merger without massive downsizing can cause negative health effects such as an changes in depression and increase in job stress. To improve the health of workers, both the immediate negative effects on health, and the long-term effects or their resolution over time should be considered prior to the merger.

Abstract Background Although recent studies have investigated the influence of vitamin D on sleep patterns, there is a lack of research on the relationship between vitamin D and sleep patterns in Korean workers. This study focused on the relationship between serum vitamin D levels and sleep in fixed day indoor field workers in the electronics manufacturing industry in Korea. Methods The 1472 subjects who were included in this study were selected from fixed day workers in the electronics manufacturing industry who had received a worker’s special health examination at a hospital in Changwon, South Gyeongsang Province between January 2015 and December 2015. Nighttime workers and those who showed symptoms of depression were excluded from this study. The sociodemographic and lifestyle variables of the participants were investigated, including age, sex, marital status, level of education, body mass index, smoking habits, alcohol consumption habits, and regular exercise. Work-related factors were evaluated, such as employee tenure and occupational stress. Serum 25-hydroxyvitamin D was measured as an indicator of vitamin D levels, and quality of sleep was evaluated using the Pittsburgh Sleep Quality Index (PSQI) translated into Korean. Results The subjects had a mean serum vitamin D level of 13.70 ± 5.93 ng/mL. Vitamin D deficiency, defined as a serum vitamin D level of