miR-122/PPARß axis is involved in hypoxic exercise and modulates fatty acid metabolism in skeletal muscle of obese rats.

Hypoxic exercise is an effective intervention for obesity, because it promotes weight loss by regulating fatty acid (FA) metabolism. The regulation of peroxisome proliferator-activated receptor ß (PPARß) by miR-122 may be involved in this process, but the detailed mechanisms are unknown. In order to address this issue, we probed how miR-122 affected the expression of factors associated with FA metabolism in skeletal muscle of obese rats undergoing hypoxic training. By injecting adeno-associated virus 9 containing miR-122 overexpression vector or miR-122 inhibitor into skeletal muscles of rats with a 4-week hypoxic exercise regimen, the miR-122 expression level can be regulated. Body composition and blood lipid levels were analyzed, and PPARß, carnitine palmitoyltransferase 1b (CPT1b), acetylCoA carboxylase 2 (ACC2), and FA synthase (FAS) mRNA and protein levels were evaluated using quantitative reverse transcription quantitative PCR(RT-qPCR) and Western blot analysis. We found that miR-122 overexpression increased low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and decreased PPARß, ACC2, and FAS expression. Conversely, miR-122 inhibition decreased TG level, increased high-density lipoprotein cholesterol (HDL-C) level, and upregulated PPARß, ACC2, FAS, and CPT1b. These data indicated that the negative regulation of PPARß by miR-122 promotes FA metabolism by altering the levels of the factors related to FA metabolism in skeletal muscle of obese rat under hypoxic training, thus providing molecular-level insight into the beneficial effects of this intervention.

Chinese Compilation of Physical Activities in healthy adults aged 18-64: Categories and metabolic intensities.

A Chinese Compilation of Physical Activities was compiled to estimate the energy costs of physical activities (PAs) using data on adults aged 18-64. Data were obtained from published articles and laboratory measurements. Databases, including PubMed, Embase, Scopus, Ebsco, Web of Science, Chinese National Knowledge Infrastructure, Wan Fang Data, National Science and Technology Report Service, Public Health Scientific Data were searched to collect data from inception to January 2022, on energy expenditure associated with PA in the healthy Chinese population. Two reviewers independently screened the literature and extracted, classified, and summarized data. Data were measured for 36 PAs using indirect calorimetry. Detailed descriptions of specific activities and metabolic equivalent values were provided by summarizing 241 physical activities in 13 categories. The first edition of the Chinese Compilation of PAs in Healthy Adults Aged 18-64(CCPA) was created. It provides valuable resources for people who regularly engage in physical exercise, researchers, educators, fitness professionals, and health or commercial sectors to quickly obtain various PA MET intensities. In the future, the energy expenditure of various PAs of different ages within the Chinese population can be measured based on the CCPA.

BAIBA Involves in Hypoxic Training Induced Browning of White Adipose Tissue in Obese Rats.

In recent years, obesity has become an important risk factor for human health; how to effectively prevent and reduce the occurrence of obesity is a hot research topic in recent years. Hypoxic training effectively improves abnormalities of lipid metabolism caused by obesity. The current study explored the effects of hypoxic training on BAIBA secretion and white fat browning in inguinal fat in obese rats. Analyses were performed by HPLC/MS/MS-MS/MS, RT-q PCR and western blot methods. The findings showed that 4 weeks of hypoxic training reduced body weight, Lee's index, and regulated blood lipid profile in obese rats. Hypoxic training up-regulated BAIBA concentration in gastrocnemius muscle and circulation in obese rats. Hypoxic training significantly upregulated expression of PPARα and UCP-1 in inguinal fat of obese rats and increased white fat browning. The findings showed that BAIBA may involve in improveing blood lipid profile and white fat browning by modulating PPARα and UCP-1 expression.

Changes in Chinese Adults' Physical Activity Behavior and Determinants before and during the COVID-19 Pandemic.

PURPOSE: To investigate the changes in Chinese adults' physical activity (PA) behavior and determinants before and during the COVID-19 pandemic. METHOD: A total of 1028 adults (aged 19-59 years) were recruited from 127 urban and rural neighborhoods in China using stratified three-stage probability sampling. Data collection was conducted in December 2019 and July 2020. RESULTS: Compared with the data before the pandemic, individuals' weekly moderate-to-vigorous-intensity PA (MVPA) decreased significantly from 139 min to 120 min, seven months after the outbreak (p = 0.01), with female and rural populations displaying a more significant decrease (p = 0.02). Overall, 13.7% of participants met the PA guidelines (World Health Organization) both before and during the pandemic, while 21.8% met the guidelines only before the pandemic and 18.1% increased their PA and met the PA guidelines during the pandemic. A total of 46.4% did not meet the PA guidelines before or during the pandemic. Determinants of PA behavior change before and during the pandemic included sports skills, self-determined motivation and support from sports organizations. CONCLUSIONS: The Chinese adults' PA levels decreased significantly from before to during the COVID-19 pandemic, particularly among the female population. It is suggested that the enhancement of self-determined motivation, improvement of sport skills, and support from sports organizations might be effective in facilitating individuals' engagement in PA during the pandemic.

Inhibition of miR-27b Regulates Lipid Metabolism in Skeletal Muscle of Obese Rats During Hypoxic Exercise by Increasing PPARγ Expression.

Hypoxic exercise may represent a novel therapeutic strategy to reduce and prevent obesity through the regulation of lipid metabolism. During hypoxic exercise, the targeting of peroxisome proliferator-activated receptor gamma (PPARγ) by miR-27b has been proposed to be one of the mechanisms involved in the modulation of lipid metabolism. We have previously shown that miR-27b can repress PPARγ and lipid metabolism-associated factors, thereby affecting lipid metabolism during hypoxic exercise in a rat model of obesity. In the current study, we aimed to confirm the role of miR-27b in the regulation of lipid metabolism. First, miR-27b expression was either upregulated or downregulated through the injection of adeno-associated virus (AAV) 9 containing a miR-27b expression cassette or miR-27b-3p inhibitor, respectively, into the right gastrocnemius muscle of obese rats. The rats were then subjected to a 4-week program of hypoxic exercise, and a series of parameters related to lipid metabolism were systematically evaluated, including body composition, blood lipid levels, miR-27b RNA levels, and mRNA and protein levels of PPARγ and those of its downstream lipid metabolism-associated factors. No significant differences were found in body composition between rats expressing different levels of miR-27b. However, regarding blood lipids, miR-27b overexpression led to increased concentrations of triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and free fatty acids (FFAs), while inhibition of miR-27b decreased the total cholesterol (TC) level and increased that of high-density lipoprotein cholesterol (HDL-C). At the mRNA level, miR-27b overexpression downregulated the expression of Pparγ, but upregulated that of lipid metabolism-associated factors such as heart-type fatty acid-binding protein (H-FABP), fatty acid transport protein 1 (FATP1), adipose triglyceride lipase (ATGL), and lipoprotein lipase (LPL), whereas miR-27b inhibition elicited the opposite effect; however, inhibition of miR-27b led to elevated cholesterol 7 alpha-hydroxylase (CYP7A1) and fatty acid translocase 36 (CD36) levels. Similarly, at the protein level, miR-27b overexpression promoted a decrease in the concentration of PPARγ, whereas miR-27b inhibition led to an increase in PPARγ levels, as well as those of CYP7A1, CD36, ATGL, and LPL. Overall, our results indicated that hypoxic exercise regulates lipid metabolism via the miR-27b/PPARγ pathway and modulates ATGL and LPL expression through inducing their post-transcriptional modifications.

Lipolysis by downregulating miR-92a activates the Wnt/ß-catenin signaling pathway in hypoxic rats.

The aim of the present study was to investigate the role of miR-92a in lipid metabolism in hypoxic rats. Microarray analysis and reverse transcription-quantitative (RT-q)PCR were used to detect changes in the mRNA expression levels of miR-92a in the epididymal fat of hypoxic and normoxic rats. The downstream target mRNA of miR-92a was predicted using bioinformatics analysis and verified using a dual luciferase reporter assay. Changes in the expression of frizzled (Fzd)10 and c-Myc in the epididymal fat were detected using RT-qPCR and western blotting. Microarray analysis and RT-qPCR results showed that the expression of miR-92a was significantly lower in the fat tissues of the hypoxic rats compared with the normoxic rats. The results of the dual luciferase reporter assay showed that the target gene of miR-92a was Fzd10, which is an acceptor in the Wnt pathway. Fzd10 expression was upregulated in the hypoxic rats. The mRNA expression levels of c-Myc, which is located downstream of the Wnt pathway, was increased significantly. The increase in the mRNA and protein expression levels of Fzd10 and c-Myc may be associated with miR-92a downregulation. Downregulation of miR-92a in-turn may result in lipolysis through the regulation of the Wnt/ß-catenin signaling pathway, and thus weight loss in the rats.

Physical activity and health in Chinese children and adolescents: expert consensus statement (2020).

China is experiencing significant public health challenges related to social and demographic transitions and lifestyle transformations following unprecedented economic reforms four decades ago. Of particular public health concern is the fourfold increase in overweight and obesity rates in the nation's youth population, coupled with the low prevalence of adolescents meeting recommended levels of physical activity. Improving the overall health of China's more than 170 million children and adolescents has become a national priority. However, advancing nationwide health initiatives and physical activity promotion in this population has been hampered by the lack of a population-specific and culturally relevant consensus on recommendations for achieving these ends. To address this deficiency and inform policies to achieve Healthy China 2030 goals, a panel of Chinese experts, complemented by international professionals, developed this consensus statement. The consensus was achieved through an iterative process that began with a literature search from electronic databases; in-depth reviews, conducted by a steering committee, of the resulting articles; and panel group evaluations and discussions in the form of email correspondence, conference calls and written communications. Ultimately, the panel agreed on 10 major themes with strong scientific evidence that, in children and adolescents aged 6-17, participating in moderate to vigorous physical activities led to multiple positive health outcomes. Our consensus statement also (1) highlights major challenges in promoting physical activity, (2) identifies future research that addresses current knowledge gaps, and (3) provides recommendations for teachers, education experts, parents and policymakers for promoting physical activity among Chinese school-aged children and adolescents. This consensus statement aligns with international efforts to develop global physical activity guidelines to promote physical activity and health and prevent lifestyle-related diseases in children and adolescents. More importantly, it provides a foundation for developing culturally appropriate and effective physical activity interventions, health promotion strategies and policy initiatives to improve the health of Chinese children and adolescents.

Effects of Living High-Training Low and High on Body Composition and Metabolic Risk Markers in Overweight and Obese Females.

This study examined the effects of 4 weeks of living high-training low and high (LHTLH) under moderate hypoxia on body weight, body composition, and metabolic risk markers of overweight and obese females. Nineteen healthy overweight or obese females participated in this study. Participants were assigned to the normoxic training group (NG) or the LHTLH group (HG). The NG participants lived and trained at sea level. The HG participants stayed for approximately 10 hours in a simulated 2300 m normobaric state of hypoxia for six days a week and trained for 2 hours 3 times a week under the same simulated hypoxia. The interventions lasted for 4 weeks. All groups underwent dietary restriction based on resting metabolic rate. The heart rate of the participants was monitored every ten minutes during exercise to ensure that the intensity was in the aerobic range. Compared with the preintervention values, body weight decreased significantly in both the NG and the HG (-8.81 ± 2.09% and -9.09 ± 1.15%, respectively). The fat mass of the arm, leg, trunk, and whole body showed significant reductions in both the NG and the HG, but no significant interaction effect was observed. The percentage of lean soft tissue mass loss in the total body weight loss tended to be lower in the HG (27.61% versus 15.94%, P=0.085). Between the NG and the HG, significant interaction effects of serum total cholesterol (-12.66 ± 9.09% versus -0.05 ± 13.36%,) and apolipoprotein A1 (-13.66 ± 3.61% versus -5.32 ± 11.07%, P=0.042) were observed. A slight increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the HG (1.12 ± 12.34%) but a decrease was observed in the NG (-11.36 ± 18.91%). The interaction effect of HDL-C between NG and HG exhibited a significant trend (P=0.055). No added effects on serum triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), or APO-B were observed after 4 weeks of LHTLH. In conclusion, 4 weeks of LHTLH combined with dietary restriction could effectively reduce the body weight and body fat mass of overweight and obese females. Compared with training and sleeping under normoxia, no additive benefit of LHTLH on the loss of body weight and body fat mass was exhibited. However, LHTLH may help to relieve the loss of lean soft tissue mass and serum HDL-C.

Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats.

Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n = 10 each): control, sedentary hypoxic living for 1-4 weeks (SH1, SH2, SH3, and SH4), living, and exercise training in normoxic conditions for 1-4 weeks (TN1, TN2, TN3, and TN4), and living and exercise training in hypoxic conditions for 1-4 weeks (TN1, TN2, TN3, and TN4). Epididymal adipose tissue expression levels of leptin and leptin receptor were determined Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P < 0.05-0.01), and higher expression of leptin and leptin receptor (P < 0.05-0.01) in adipose tissue. Conclusion: In a rodent model of altitude training, living, and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

Apoptosis and inhibition of proliferation of cancer cells induced by cordycepin.

Cordycepin, a 3-deoxyadenosine, is the predominant functional component of the fungus Cordyceps militaris, a traditional Chinese medicine. Previous studies investigating the inhibition of cancer cells by cordycepin identified that it not only promotes cell apoptosis, but also controls cell proliferation. Furthermore, studies have elucidated the molecular mechanisms of inhibiting cell proliferation by cordycepin binding the A3 adenosine receptor, activating G protein, inhibiting cAMP formation, decreasing glycogen synthase kinase-3ß/ß-catenin activation and suppressing cyclin D1 and c-myc expression. The most significant signaling pathway in which cell apoptosis is induced by cordycepin is the caspase pathway. Cordycepin induces cell apoptosis via binding the DR3 receptor and consequently activating caspase-8/-3. Taken together, these studies demonstrate that cordycepin may be used as a natural medicine, as it can not only control tumor cell proliferation, but also induce cancer cell apoptosis.

Effects of hypoxic exercise training on microRNA expression and lipid metabolism in obese rat livers.

To investigate the effects of hypoxic exercise training on microRNA (miRNA) expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group (N, n=10) and a hypoxic exercise training group (H, n=10). After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of peroxisome proliferator activated receptor α (PPARα), fatty acid synthetase (FAS), and carnitine palmitoyl transferase 1A (CPT1A) in rat liver. Body weight, Lee's index, fat mass, fat/weight ratio, and serum levels of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were all significantly lower in the H group than in the N group (P<0.01). Six miRNAs expressed significantly differently in the liver (P<0.05). Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group (P<0.05). Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPT1A mRNA (P<0.05), as well as lower CPT1A protein levels (P<0.01), while a higher ratio of FAS to CPT1A protein levels (P<0.01) was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPT1A and increasing the protein expression ratio of FAS/CPT1A.

Effects of hypoxic living and training on gene expression in an obese rat model.

PURPOSE: The study's purpose was to determine in a rat obesity model the effects of normoxic training, sedentary hypoxic living, or hypoxic living plus training on the skeletal muscle messenger RNA (mRNA) levels of 14 genes involved in oxygen sensing (hypoxia-inducible factor 1α, vascular endothelial growth factor, myoglobin), glucose metabolism (glucose transporter 4, muscle phosphofructokinase), mitochondrial biogenesis (peroxisome proliferator-activated receptor γ coactivator 1-α, nuclear respiratory factor 1) and function (citrate synthase, mitochondrial-encoded cytochrome oxidase subunit 1), pH regulation (monocarboxylate transporter 1, carbonic anhydrase 3), and antioxidant defense (manganese superoxide dismutase, copper/zinc superoxide dismutase, glutathione S-transferase pi). METHODS: One hundred thirty male 3-wk-old Sprague-Dawley rats were fed a high-fat diet (4100 kcal·kg(-1)) for 3 months (all reaching a final weight >415 g) and then randomly assigned to the following groups (n = 10 per group): C (control, 2 d of sedentary living in normoxic conditions), TN1-TN4 (1-4 wk of normoxic treadmill training), SH1-SH4 (1-4 wk of sedentary hypoxic living (13.6% O2)), or TH1-TH4 (1-4 wk of hypoxic living (13.6% O2) + hypoxic treadmill training). Individual mRNA levels recorded for TN1-TN4, SH1-SH4, and TH1-TH4 were expressed relative to the mean obtained in C for each gene. RESULTS: Through a two-way ANOVA, a significant interaction (treatment × treatment duration) effect was detected on expression levels of mRNAs for hypoxia-inducible factor 1α, vascular endothelial growth factor, myoglobin, nuclear respiratory factor 1, citrate synthase, carbonic anhydrase 3, monocarboxylate transporter 1, copper/zinc superoxide dismutase, glutathione S-transferase pi, and manganese superoxide dismutase. Expression levels were overall highest when training and living under hypoxia, usually after 3 wk (TH3), i.e., 79%-99% higher than the lowest values (usually corresponding to TN2) and 15.5%-53.9% higher than the second highest values (usually TH4). Normoxic training elicited no greater response than hypoxic sedentary living. CONCLUSIONS: In our obese rat model, hypoxic living conditions, especially if accompanied by hypoxic exercise training, can lead to health-related molecular adaptations at the skeletal muscle level.

Association between HMOX-1 genotype and cardiac function during exercise.

The human gene for heme oxygenase-1 (HMOX-1) plays an important role in the regulation of cardiovascular function and its adaptive response to a variety of stressors. The purpose of this study was to examine the possible association between HMOX-1 genotypes (for -1135A/G, -413A/T, and rs5755720 polymorphisms) and cardiac structural and functional parameters at rest and during submaximal cycle-ergometer exercise (50, 100, and 150 W) in a pre-training state (baseline) and after endurance training (18 weeks, 95%~105% individual ventilatory threshold). The study population consisted of 102 Chinese young males (non-athletes) of Han origin. For the -1135A/G polymorphism, we found a significant genotype effect (p < 0.05) in cardiac output (Q) corrected for body surface area (BSA; Q.BSA(-1)) at 50 W and stroke volume (SV) corrected for BSA (SV.BSA(-1)) at 100 W. For the -413A/T polymorphism, we found a significant genotype effect (p < 0.05) in ejection fraction (EF) at 100 W. For the rs5755720 polymorphism, we found a significant genotype effect (p < 0.01 or p < 0.05) in most variables (Q.BSA-1 across all workloads, SV.BSA(-1) at 100 W, and EF at 50 and 100 W). Briefly, rs5755720 individuals with a CC genotype presented overall higher values in the different cardiac variables than their CT and (or) TT counterparts. In summary, although more research is needed with diseased populations and other ethnic groups, we found preliminary evidence of an association between cardiac response to submaximal exercise and HMOX-1 genotype. The present preliminary findings could provide insights to future studies searching for cardioprotective genotypes.

[Alterations of erythrocyte deformability and membrane protein after high intensity training and recovery in rats].

AIM AND METHODS: The purpose of this investigation was to determine the changes of erythrocyte deformability, band-3 protein and actin in the definite volume of erythrocyte membrane after high intensity running training and recovery in rats. RESULTS: Long-term training could significantly improve erythrocyte deformability and the quantity of membrane proteins. Erythrocyte deformability, band-3 protein and actin decreased transitorily at varying degrees after inadaptable high intensity exercise. One and two week training could improve erythrocyte deformability, the quantity of band-3 protein and actin after recovery. CONCLUSION: Alterations of erythrocyte membrane protein after high intensity training could cause the change in erythrocyte membrane structure and hence influenced erythrocyte deformability. That was maybe one of mechanisms of training effecting erythrocyte deformability.