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Exercise training has been demonstrated as an effective therapy for insulin resistance (IR) to relieve skeletal muscle metabolic disorders. Physiologic protective autophagy was found blocked by IR induced severe endoplasmic reticulum (ER) stress, which may lead to progression of IR. However, the mechanisms are not fully understood. Therefore, this study sought to investigate that how exercise training act on IR through an exploration into the mechanism of ER stress and high-fat diet (HFD)-blocked autophagy. A rodent model was adopted in mice via a HFD and an 8-week swim exercise training intervention. The mouse IR model was successfully established through HFD treatment: body mass, adipose weight, HOMA-IR index increased, as well as IRS1, inhibited in the muscle of HFD mice. Moreover, the AMPK/PGC1α pathway was depressed and IRE1, PERK, ATF6-related ER stress signaling was activated in the muscle of HFD mice. While autophagy factors, including BNIP3, LC3II/LC3I, and PINK1, decreased. However, additional 8-week exercise training during HFD was found to reverse all these changes and alleviate IR. Thus, exercise training could facilitate HFD-blocked protective autophagy via the activation of the AMPK/PGC1α pathway to relieve insulin resistance in mice. Our study provides experimental data for the prevention of T2DM and insulin resistance.

Obesity induces skeletal muscle dysfunction. The pathogenesis of which appears to substantially involve mitochondrial dysfunction, arising from impaired quality control. Exercise is a major therapeutic strategy against muscle dysfunction. Trimetazidine, a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, the effects of Trimetazidine on regulating skeletal muscle function are largely unknown. Our present study used cell culture and obese mice models to test a novel hypothesis that Trimetazidine could improve muscle atrophy with similar results to exercise. In C2C12 cells, high palmitic acid-induced atrophy and mitochondrial dysfunction, which could be reversed by the treatment of Trimetazidine. In our animal models, with high-fat diet-induced obesity associated with skeletal muscle atrophy, Trimetazidine prevented muscle dysfunction, corrected metabolic abnormalities, and improved mitochondrial quality control and mitochondrial functions similarly to exercise. Thus, our study suggests that Trimetazidine successfully mimics exercise to enhance mitochondrial quality control leading to improved high-fat diet-induced muscle dysfunction.

Background Reference values of cardiopulmonary exercise testing (CPX) vary with race/ethnicity. Chinese Americans are the fastest-growing racial/ethnic group in the United States. However, there is limited information about the reference values of cardiopulmonary exercise testing (CPX) variables in the Chinese population. Methods As part of the Xiangya Hospital Exercise Testing project (the X-ET project), this cross-sectional study screened 20,696 consecutive CPXs performed by 17,802 unique individuals at Xiangya Hospital of Central South University, China, from January 1, 2002, to December 31, 2019. A total of 964 unique healthy adults/tests (42% female) aged 49 ± 12 who completed a maximal ramp incremental CPX with cycle ergometry were included in this study. The reference values of primary CPX variables were expressed as the lower limit or upper limit of normal. Stepwise linear regression was used to fit the equations of key CPX variables. Predictive accuracy analysis for the equations with a comparison between present and previous studies were performed. Results Peak oxygen consumption ( V O2), carbon dioxide production, ventilation/min, work rate, and V O2 at the anaerobic threshold were regressed on age, height, weight, and sex. These predictive equations showed good in- and out-sample predictive accuracy. Comparison with prior research revealed that prediction equations of peak V O2 resultant from studies in which populations were entirely or primarily Caucasian had overestimated our subjects' actual values. Conclusion The reference values and predicted equations of CPX variables in this study may provide a more appropriate framework to interpret the response to maximal ramp incremental cycle ergometry in the Chinese adult population.

Background Patients appear to maintain sequelae post-coronavirus disease 2019 (COVID-19) affecting daily life and physical health. We investigated the changes in and the effects of pulmonary rehabilitation (PR) on exercise capacity and immunology six months after COVID-19 hospitalization. Methods This retrospective cohort reviewed 233 COVID-19 patients admitted from 17 January 2020 to 29 February 2020. Ninety-eight patients who completed 2-week and 6-month follow-ups and tests were included. Among 98 patients, 27 completed at least five sessions of PR at the First Hospital of Changsha, China, during the 6-month convalescence were allocated to the PR group; the reminder who had not performed any PR were assigned to the control group. The primary outcome was the change in six-minute walk distance (6-MWD) between the 2-week and 6-month follow-ups, which was assessed via analysis of covariance with a covariate of propensity score that adjusted for the potential confounders. Secondary outcomes were the changes in 6-MWD, SARS-CoV-2 immunoglobulins, T-lymphocytes and blood chemistry, which were evaluated via paired tests. Results Participants’ ages ranged from 19 to 84 years (M = 47, standard deviation (SD)=15) 45.9% identified as male. During the 6-month convalescence, 6-MWD increased 27.0%, with a mean [95% CI] of 113 [92–134] m (p

Background the Xiangya Hospital circuit training (X-CircuiT), was developed to reverse pre-frailty in Chinese older adults and determine potential mechanisms through which pre-frailty is reversed. Methods this randomised controlled trial was performed at Xiangya Hospital, Changsha, China from September 2020 to May 2021. Forty-eight pre-frail older adults were enrolled. Participants were randomly assigned (1:1) to X-CircuiT (46 min/session, three supervised sessions/week for 3 months at a community health centre) or control (1-time advice on physical activity without supervised exercise). The primary outcome was the proportion of participants with pre-frailty after 3-month intervention. The secondary outcomes included absolute risk reduction (ARR), number needed to treat (NNT), and the changes in senior fitness, body composition and clinical measures. Results among 48 participants (mean age, 72 years; women [65%]), 22 participants in the X-CircuiT (92%) and 21 participants in the control (88%) completed the study. After 3 months, the proportion of pre-frailty was significantly lower in the X-CircuiT group than the control (14% versus 95%, P Conclusion this study demonstrates that X-CircuiT could significantly reverse pre-frailty in Chinese older adults. The underlying mechanisms may involve X-CircuiT-induced improvements in body composition and senior fitness. The trial is registered at Chictr.org.cn. Number: ChiCTR2100048125.

Rhodiola was found to be a potential treatment for nonalcoholic fatty liver disease (NAFLD). The macrophage migration inhibitory factor (MIF)-regulated lipophagy and lipid metabolism might be the therapeutic targets of Rhodiola.A 16-week high-fat diet (HFD) was used to simulate a NAFLD mouse model. Rhodiola extract or normal saline were administrated to mice. Blood was collected to assess blood glucose and insulin, and livers were harvested to assess lipid accumulation and metabolism. In cell experiments, the active ingredient of Rhodiola, salidroside, and recombinant MIF protein (rMIF) were used to treat palmitate (PA)-incubated HepG2 cells, with MIF-siRNA or NC-siRNA transfection. Then, the level of lipophagy and lipid metabolism was examined.Rhodiola improved lipid accumulation and metabolism disorder of HFD mice. The oil red O staining of the liver showed that increased lipid droplets in the NAFLD liver could be relieved by Rhodiola; Rhodiola also alleviated the increasing body weight, liver weight, and HOMA-IR index of HFD mice. Results in cell experiments were consistent: salidroside relieved the lipid droplet accumulation and triglyceride release in PA cells, as well as reduced lipophagosome and lipid metabolism disorder in PA cells. However, all these effects of salidroside were partially blocked by MIF-siRNA transfection.Rhodiola reduces lipid accumulation in the liver of NAFLD by facilitating the MIF pathway and the downstream lipophagy and lipid metabolism. MIF may be an endogenous regulator of liver lipophagy and lipid metabolism and a potential therapeutic target for NAFLD.

ObjectivesTo observe the weight change in Chinese youth during a 4-month COVID-19 lockdown, and the association between weight change and mental health, physical activity and sedentary time changes, and dietary habits.DesignA retrospective observational study.SettingsTwo universities located in Zhejiang and Hunan provinces, China.ParticipantsThis study enrolled 12 889 college students whose body weight was measured before the lockdown (1 December 2019–20 January 2020) at the two universities, and reported their weight measured at home or community after the end of the lockdown (1–23 May 2020) via an online follow-up questionnaire.Primary and secondary outcome measuresThe primary outcome was the weight change in Chinese youth during a 4-month lockdown resulting from the COVID-19 pandemic. The secondary outcomes were the relationships of weight change to COVID-19-related stress, depression, anxiety, physical activity and sedentary time changes, and dietary habits.ResultsParticipants’ ages ranged from 17 to 27 years (M=19, SD=1) with 80.2% identified as female. The average absolute and relative changes in body weight were 2.6 (95% CI 2.0 to 3.2)) kg and 4.2% (95% CI 4.0% to 4.3%) for men, and 2.1 (1.9 to 2.4) kg and 4.2% (95% CI 3.9% to 4.4%) for women. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in men and women, respectively (PConclusionThe present study’s results suggest that the risk of weight gain in Chinese youth during the lockdown increased and that strategies to decrease sedentary time and improve mental health may be warranted to mitigate weight gain during and after the COVID-19 pandemic.

Background The COVID-19 pandemic has led to a spike in deleterious mental health. This dual-center retrospective cross-sectional study assessed the prevalence of depression in young adults during this pandemic and explored its association with various physical fitness measures. Methods This study enrolled 12,889 (80% female) young adults (mean age 20 ± 1) who performed a National Student Physical Fitness battery from December 1st, 2019, to January 20th, 2020, and completed a questionnaire including Beck’s Depression Inventory in May 2020. Independent associations between prior physical fitness and depression during the pandemic were assessed using multivariable linear and binary logistic regressions accordingly, covariates including age, dwelling location, economic level, smoking, alcohol, living status, weight change, and exercise volume during the pandemic. Sex- and baseline stress-stratified analyses were performed. Results Of the study population 13.9% of men and 15.0% of women sampled qualified for a diagnosis of depression. After multivariable adjustment, anaerobic (mean change 95% CI −3.3 [−4.8 to 1.8]) aerobic (−1.5 [−2.64 to −0.5]), explosive (−1.64 [−2.7 to −0.6]) and muscular (−1.7 [−3.0 to −0.5]) fitness were independently and inversely associated with depression for the overall population. These remained consistent after sex- and baseline stress-stratification. In binary logistic regression, the combined participants with moderate, high or excellent fitness also showed a much lower risk compared to those least fit in anaerobic (odd ratio (OR) 95% CI 0.68 [0.55–0.82]), aerobic (0.80 [0.68–0.91]), explosive (0.72 [0.61–0.82]), and muscular (0.66 [0.57–0.75]) fitness. Conclusions These findings suggest that prior physical fitness may be inversely associated with depression in young adults during a pandemic.

IntroductionInsulin resistance (IR) plays a key role in the pathogenesis and clinical course of patients with multiple metabolic diseases and diabetes. This study aimed to explore the effect of trimetazidine (TMZ) on skeletal muscle IR in mice fed a high-fat diet (HFD) and explore the possible underlying mechanism.Research design and methodsIn vivo, a HFD mouse IR model was adopted and TMZ and exercise were used to intervene. Postintervention the following were determined: blood levels of glucose and insulin, homeostasis model assessment of IR index, expression of skeletal muscle insulin signaling-related proteins phosphorylated insulin receptor substrate 1 (p-IRS1/IRS1) and phosphorylated protein kinase B (p-AKT/AKT), nuclear factor erythroid 2 related factor 2 (Nrf2) signaling pathway, and oxidative stress. In vitro, a palmitate-treated C2C12 myotube IR model was constructed. Cellular glucose uptake, p-IRS1/IRS1, and p-AKT/AKT were determined, and reactive oxygen species (ROS) production was analyzed based on treatments with specific small interfering RNA of Nrf2 with or without TMZ. Western blot was used to obtain the protein expression level and ROS production by functional analysis kits.ResultsIn vivo, TMZ and exercise decreased the blood glucose and insulin levels and homeostasis model assessment of IR index, increased skeletal muscle insulin signaling-related protein ratios of p-IRS1/IRS1 and p-AKT/AKT, and both interventions activated Nrf2 signaling and reduced oxidative stress production in HFD mice. In vitro, TMZ reduced the oxidative stress reaction, increased the ratios of p-AKT/AKT and p-IRS1/IRS1, and attenuated the insulin stimulation of PA-induced glucose uptake. However, in the absence of Nrf2, TMZ failed to resist the effects of IR.ConclusionsThis study showed that TMZ, like exercise, brought about marked improvements to HFD-induced skeletal muscle IR through TMZ, a common pathway with exercise in the form of Nrf2, regulating oxidative stress. We provide new evidence to support the use of TMZ for diabetes treatment.

Background: Anti-stress capacity is important to resist the occurrence of adverse events. To observe the effects of exercise, trimetazidine alone or combined on the anti-stress capacity of mice, and further explore its potential mechanism. Methods: Forty-four C57BL/6 male mice aged 8 weeks were randomly divided into four groups (n=11 for each group): control group (group C), exercise group (group E), trimetazidine group (group T), exercise combined with trimetazidine group (group TE). After the intervention, each group was randomly subdivided into the exhaustive exercise (EE, n=6) and the non-EE (n=5) subgroups. The mice in the EE-subgroup underwent EE. Mice were sacrificed 12 hours later after EE. The myocardial ultrastructure and autophagosomes were observed under an electron microscope. The expression of autophagy-related proteins: BNIP3, LC3-II, and P62 were analyzed and the heat shock protein 70 mRNA transcription and protein expression were also investigated. Results: Exercise or trimetazidine increased the expression of BNIP3, LC3-II, and heat shock protein 70, decreased the expression of P62 pre- and post-EE while the combination has the synergistic effect. Conclusion: Exercise and trimetazidine, alone or combined enhanced the anti-stress capacity of mice significantly. The underlying mechanism may be associated with the promotion of autography and the expression of heat shock protein 70.

Highlights • Study on the immunological changes in COVID-19 patients during 3-Month Follow-up; • Antibiotics use during hospital stay was related to a decrease in IgG after discharge; • Glucocorticoid intake was associated with an increase in CD4+T cell after discharge., Background Understanding the immunological responses in COVID-19 patients during their recovery period is essential to the development of a vaccine and herd immunity. Methods This retrospective cohort study screened 233 patients admitted to the First Hospital of Changsha, China with COVID-19 from January 17th to February 29th, 2020. After completion of SARS-CoV2-specific immunoglobulins, and T cells tests at 2-week and 3-month follow-up points after discharge, 87 were enrolled. Wilcoxon signed-rank test was performed to assess changes in the values of IgG and IgM, the number of CD3+, CD4+ and CD8+ T cells, and CD4+/CD8+ ratio during the 3-month follow-up. Linear regressions were used to evaluate the associations of immunological changes and medications during hospitalization. Results The positive rate of IgG decreased from 98.6% (40/41) to 85.4% (35/41) in men and 100% (43/43) to 76.7% (33/43) in women, whereas IgM declined from 34.1% (14/41) to 12.2% (5/41) in men and 37.2% (16/43) to 27.9% (12/43) in women during the follow-up. CD4+ T cells increased from (median (IQR), 484 (384-635)) cells/ul to 543 (414-657) cells/ul (P=0.01). Antibiotic use was negatively associated with IgG change (mean change [95%CI], 8.08 [0.80 to 15.37] U, P=0.03), and glucocorticoid use was positively related to increased CD4+ T cells (100.85 [16.56 to 185.15] cells/ul, P=0.02). Conclusion This study demonstrated that the positive rates and values of IgG and IgM decreased in COVID-19 patients over a 3-month follow-up, while CD4+ T cells significantly increased. Moreover, we found that antibiotic use during hospitalization was associated with IgG decrease, and glucocorticoid use was associated with increases in CD4+ T cells.

Aim To emphasize the mechanism of the effect of exercise on lipid droplet (LD) metabolism disorder in nonalcoholic fatty liver disease (NAFLD). Main methods C57BL/6J mice were randomly divided into three groups: The first group was fed with a normal diet (CON), the second group was fed a high-fat diet (HF), and finally group with a high-fat diet intervention and swim training (HF-EX). The total intervention period was 16 weeks. RT-PCR and Western blot were performed to evaluate the effect of exercise on LDs metabolism and the AMPK pathway. Histopathological examinations and immunofluorescence were performed to evaluate the lipid deposition and lipophagy in the liver. Key findings Exercise reduced liver steatosis and insulin resistance along with the stimulation of AMPK/SIRT1 signaling and downstream regulation of lipid metabolism. In addition, exercise increased the expression of autophagy marker and colocalization of LC3 and LAMP1 with LDs. Significance Exercise stimulated AMPK/SIRT1 and activated lipophagy in NAFLD. Enhancing lipophagy may be one of the key mechanisms of regulation and resolution of NAFLD by exercise.