Adipose Tissue Macrophage Polarization Is Altered during Recovery after Exercise: A Large-Scale Flow Cytometric Study.

We performed a large-scale flow cytometric analysis to determine whether M1 macrophage (M1Ø) and M2 macrophage (M2Ø) polarization in white adipose tissue (WAT) was altered immediately after exercise. Additionally, we comprehensively investigated the effects of obesity, exercise intensity, and recovery time on macrophage polarization in WAT. A single exercise bout of various intensities (ND, non-exercise control; -LIE, low-intensity exercise; -MIE, mid-intensity exercise; -HIE, high-intensity exercise) was performed by normal mice (ND) and obese mice (HFD). To confirm differences in M1Ø/M2Ø polarization in WAT based on the recovery time after a single exercise bout, WAT was acquired at 2 h, 24 h, and 48 h after exercise (total n = 168, 7 mice × 4 groups × 2 diets × 3 recovery time). The harvested WAT was immediately analyzed by flow cytometry, and macrophages were fluorescently labeled using F4/80, as well as M1Ø with CD11c and M2Øs with CD206. After a single bout of exercise, the M2Ø/M1Ø polarization ratio of WAT increases in both normal and obese mice, but differences vary depending on recovery time and intensity. Regardless of obesity, our findings showed that there could be a transient increase in M1Ø in WAT over a short recovery time (24 h) post-exercise (in ND-MIE, ND-HIE, and HFD-HIE). Furthermore, it was observed that the greater the exercise intensity in obese mice, the more effective the induction of M2Ø polarization immediately after exercise, as well as the maintenance of high M2Ø polarization, even after a prolonged recovery time.

Demographic and Genome Wide Association Analyses According to Muscle Mass Using Data of the Korean Genome and Epidemiology Study.

BACKGROUND: Sarcopenia is commonly found in the elderly due to a decline in muscle mass. Many researchers have performed genome-wide association studies (GWAS) to find genetic risk factors of sarcopenia. Although many studies have discovered sarcopenia associated single nucleotide polymorphisms (SNPs), most of them are studies targeting Caucasians. The purpose of this study was to evaluate genetic correlation according to muscle mass in middle aged Koreans using data of the Korean Genome and Epidemiology Study (KOGES), a large population-based genomic cohort study. METHODS: Baseline participants were 10,030 subjects aged 40 to 69 years who were from Ansan or Anseong in Gyeonggi-do, South Korea. Among them, 9,351 subjects with laboratory data available were included in this study. To identify sarcopenia associated variants, those in the top 30% and bottom 30% of muscle mass index (MMI) were compared. A total of 7,452 people with an MMI of 30-70% were excluded. A total of 1,004 people were also excluded due to missing data. Finally, 895 people were selected for this study. The Korea Biobank Array generated 500,568 SNPs for this dataset. RESULTS: When subjects were divided into top 30% and bottom 30% of MMI, the top 30% had 169 men and 308 women and the bottom 30% had 220 men and 198 women. In men, age, body mass index (BMI), waist and hip were significantly (P < 0.005) different between top 30% and bottom 30% MMI groups. In women, age, BMI, waist, hip, and hypertension history were significantly different between the two MMI groups. There were 13 significant SNPs in men and 14 significant SNPs in women. Genes associated with variants in men based on the single-nucleotide polymorphism database (dbSNP) were LRP1B containing rs11679458 and RGS6 containing rs11848300. A gene associated with variants in women was Pi4K2A, which contained rs1189312 as a variant. In addition, rs11189312 was associated with expression quantitative trait loci (eQTL) of ZFYVE27 in skeletal muscles and other SNPs of ZFYVE27 (rs10882883, rs17108378, rs35077384) known to be associated with spastic paraplegia. The eQTL analysis revealed that rs11189312 was a variant associated with SNPs of ZFYVE27. CONCLUSIONS: In the demographic study, significant results were found in BMI, waist, hip, history of hyperlipidemia, and sedentary life status in male group, and significant results were found in BMI, waist, hip, and hypertension history in female group. Variant rs11189312 was found to be a novel variant affecting ZFYVE27 expressed in skeletal muscles, suggesting that rs11189312 might be related to sarcopenia as a novel discovery of this study. Further study is needed to determine the association between sarcopenia and ZFYVE27 known to be associated with spastic paraplegia.

Comparative analysis of the association between various serum vitamin D biomarkers and sarcopenia.

BACKGROUND: Vitamin D status is associated with muscle strength and maintenance of muscle fibers. However, which serum vitamin D biomarker better reflects sarcopenia remains unclear. The aim of this study was to investigate associations between various serum vitamin D biomarkers (total 25-hydroxy vitamin D [25(OH)D], bioavailable 25(OH)D, 24,25-dihydroxyvitamin D [24,25(OH)2 D], and vitamin D metabolite ratio [VMR]) and sarcopenia. METHODS: The data for 83 hip fracture patients were finally included in the analysis. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria. Measurements of 24,25(OH)2 D and 25(OH)D were made using solid-phase extraction (SPE) and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS). Vitamin D binding protein (VDBP) concentration was measured using an enzyme-linked immunosorbent assay. The VMR was calculated by dividing serum 24,25(OH)2 D by serum 25(OH)D and then multiplying by 100. Based on total 25(OH)D, VDBP, and albumin concentrations, bioavailable 25(OH)D concentrations were calculated using the equations from the other previous studies. RESULTS: Bioavailable 25(OH)D levels were significantly (p = 0.030) decreased in the sarcopenia group compared with the non-sarcopenia group. Results of ROC analysis for the diagnosis of sarcopenia using serum level of bioavailable of 25(OH)D revealed that the cutoff point for bioavailable 25(OH)D was 1.70 ng/ml (AUC = 0.649, p < 0.001). In the group with a bioavailable 25(OH)D less than 1.70 ng/ml, the incidence of sarcopenia increased by 3.3 times (odds ratio: 3.33, p = 0.013). CONCLUSION: We demonstrated that bioavailable 25(OH)D was associated with sarcopenia among the various serum vitamin D biomarkers. Bioavailable vitamin D might be helpful for assessing the risk of sarcopenia.

Exercise training reduces the risk of opportunistic infections after acute exercise and improves cytokine antigen recognition.

In general, acute exercise is thought to inhibit immune function and increase the risk of opportunistic infections, but there is some opposition to this due to a lack of quantitative evaluation. Therefore, we quantified the effect of exercise on immune function and observed the interaction between antigens and cytokines using an intramuscular infection with Trichinella spiralis (T. spiralis), a common parasitic infection model. C57BL/6 mice were used for a non-infection experiment and an infection (Inf) experiment. Each experiment was divided further into three groups: one control (CON) group, and an exercise pre-infection (PIE)-only group and exercise-sustained (ES) group, each of which was subjected to exercise for 7 weeks. All animals in the infection experiment were infected with T. spiralis 30 min after acute exercise. After infection, the ES and Inf-ES groups continued exercise for 7 additional weeks. The number of T. spiralis nurse cells remaining in skeletal muscles was fewer in the infected exercise groups compared with the infected control. Expression of interleukin-6 (IL-6) and interleukin-10 (IL-10) was higher in the Inf-CON group and transforming growth factor beta (TGF-ß) expression was lower in the Inf-CON group than in the CON group, as measured by RT-PCR. In the infection experiment, only IL-10 had significant differences between the groups. Immunofluorescence revealed that most cytokines were specifically expressed around the antigenic nurse cells following exercise. In conclusion, exercise training does not increase the risk of opportunistic infections even after acute exercise, but rather reduces it. These results may be due to antigen-specific immune responses.

Induction of Angiogenesis by Malarial Infection through Hypoxia Dependent Manner.

Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of HIF1α through an intracellular oxygen-sensing pathway. Activation of HIF1α may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infection actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of 2×106 parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors including VEGF and HIF1α. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tissues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and HIF1α increased with the parasitemia in various tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxia-induced angiogenesis by stimulation of HIF1α and VEGF in various tissues.

Effect of Muscle Strength by Trichinella spiralis Infection during Chronic Phase.

Introduction:Trichinella spiralis establishes a chronic infection in skeletal muscle by developing nurse cells within muscle fibers. During symbiosis in host, changes in the muscle fibers and inflammation may affect muscle function. Methods: We investigated muscle strength and inflammation in T. spiralis-infected mice during 1 to 48 weeks after infection. Results: Muscle strength decreased compared to that in uninfected control mice during the late infection stage. Additionally, inflammatory related cytokines increased significantly during early stage of infection and then rapidly decreased. In pathological study, nuclear infiltration maintained from the early infection stage to chronic infection stage. Moreover, vacuoles and eosinophil infiltration were observed in infected muscle in chronic stage. Conclusion: These results suggest that infection by T. spiralis significantly affects muscle function was continuously being weakness because vacuoles formation and maintained nucleus and eosinophil infiltration during chronic phase of T. spiralis infection.

The Effect of Exercise on Mesenchymal Stem Cells and their Application in Obesity Treatment.

Mesenchymal stem cells (MSCs) have demonstrated considerable potential in tissue repair and the treatment of immune-related diseases, but there are problems with homing efficiency during MSCs transplantation. Exercise, as an intervention, has been shown to have an important impact on the properties of MSCs. This review summarizes the effects of exercise on the properties (including proliferation, apoptosis, differentiation, and homing) of bone marrow-derived MSCs and adipose-derived MSCs. Studies indicated that exercise enhances bone marrow-derived MSCs proliferation, osteogenic differentiation, and homing while reducing adipogenic differentiation. For adipose-derived MSCs, exercise enhances proliferation and reduces adipogenic differentiation. In addition, studies have investigated the therapeutic effects of combined therapy of MSCs transplantation with exercise on diseases of the bone, cardiac, and nervous systems. The combined therapy improves tissue repair by increasing the homing of transplanted MSCs and cytokine secretion (such as neurotrophin 4). Furthermore, MSCs transplantation also has potential for the treatment of obesity. Although the effect is not significant in weight loss, MSCs transplantation shows effects in controlling blood glucose, improving dyslipidemia, reducing inflammation, and improving liver disease. Finally, the potential role of combined MSCs transplantation and exercise therapy in addressing obesity is discussed.

Exercise intensity impacts the improvement of metabolic dysfunction-associated steatotic liver disease via variations of monoacylglycerol O-acyltransferase 1 expression.

BACKGROUND: The involvement of monoacylglycerol O-acyltransferase 1 (MOGAT1) in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) has been recognized. While exercise is recommended for the improvement of obesity and MASLD, the impact of exercise intensity remains unclear. This study aimed to examine the influence of exercise intensity on MOGAT1 expression in high-fat diet (HFD)-induced obese mice with MASLD. METHOD: Male C57BL/6 mice aged 6 weeks were subjected to either a regular or HFD with 60 % fat content for 8 weeks. The mice were categorized into 5 groups based on their diet and exercise intensity: normal diet group (ND), HFD group, low-intensity exercise with HFD group (HFD+LIE), moderate-intensity exercise with HFD group (HFD+MIE), and high-intensity exercise (HIE) with HFD group (HFD+HIE). The duration of running was adjusted to ensure uniform exercise load across groups (total distance = 900 m): HFD+LIE at 12 m/min for 75 min, HFD+MIE at 15 m/min for 60 min, and HFD+HIE at 18 m/min for 50 min. RESULTS: Lipid droplet size and MASLD activity score were significantly lower in the HFD+HIE group compared to other exercise-intensity groups (p < 0.05). Among the 3 intensity exercise groups, the lowest MOGAT1 protein expression was found in the HFD+HIE group (p < 0.05). CONCLUSION: This study reveals that high-intensity exercise has the potential to mitigate MASLD development, partly attributed to the downregulation of MOGAT1 expression.

Epigenome-wide Association Study for Tic Disorders in Children: A Preliminary Study in Korean Population.

Objective: : Tic disorders can affect the quality of life in both childhood and adolescence. Many factors are involved in the etiology of tic disorders, and the genetic and epigenetic factors of tic disorders are considered complex and heterogeneous. Methods: : In this study, the differentially methylated regions (DMRs) between normal controls (n = 24; aged 6-15; 7 females) and patients with tic disorders (n = 16; aged 6-15; 5 females) were analyzed. We performed an epigenome-wide association study of tic disorders in Korean children. The tics were assessed using Yale Global Tic Severity Scale. The DNA methylation data consisted of 726,945 cytosine phosphate guanine (CpG) sites, assessed using the Illumina Infinium MethylationEPIC (850k) BeadChip. The DNA methylation data of the 40 participants were retrieved, and DMRs between the four groups based on sex and tic disorder were identified. From 28 male and 16 female samples, 37 and 38 DMRs were identified, respectively. We analyzed the enriched terms and visualized the network, heatmap, and upset plot. Results: : In male, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed hypomethylated patterns in the ligand, receptor, and second signal transductors of the PI3K-Akt and MAPK signaling pathway (most cells were indicated as green color), and in female, the opposite patterns were revealed (most cells were indicated as red color). Five mental disorder-related enriched terms were identified in the network analysis. Conclusion: : Here, we provide insights into the epigenetic mechanisms of tic disorders. Abnormal DNA methylation patterns are associated with mental disorder-related symptoms.

The protective effect of IL-12/23 neutralizing antibody in sarcopenia associated with dextran sulfate sodium-induced experimental colitis.

BACKGROUND: The improvement of colitis symptoms by treatment with IL-12/23 p40 neutralizing antibody should increase the muscle mass and the function of the sarcopenia phenotype. METHODS: An experimental colitis model was induced by oral administration of 2% dextran sulfate sodium (DSS) for 7 days. During induction of colitis, IL-12/23 p40 neutralizing antibody was injected twice on Days 3 and 5. The total body mass index was measured by dual-energy X-ray absorptiometry. The muscle function was measured by forelimb grip strength and fatigue running distance. The muscle fibre cross-sectional area (CSA) was calculated after the transverse section and haematoxylin and eosin staining, and gene expression was confirmed by RT-qPCR. Differentiated C2C12 cells were used as in vitro models and treated with recombinant IL12/23 proteins to mimic the enhanced cytokines in colitis. RESULTS: The symptoms of colitis were alleviated by injection of IL-12/23 p40 neutralizing antibody compared with phosphate-buffered saline (PBS), and the disease activity index score was significantly lower on Day 8 (0.0 ± 0.00 of cont. vs. 11.3 ± 0.9 of DSS + PBS, P < 0.0001; DSS + PBS vs. 7.7 ± 1.25 of DSS + p40Ab, P < 0.0001). The CSA of the gastrocnemius and tibialis anterior muscle fibres decreased in mice with DSS-induced colitis (gastrocnemius, 1258.2 µm2 ± 176.45 of cont. vs. 640.1 µm2 ± 59.83 of DSS + PBS, P < 0.0001; tibialis anterior, 1251.8 µm2 ± 331.48 of cont. vs. 678.9 µm2 ± 67.59 of DSS + PBS, P < 0.0001), and the treatment of IL-12/23 p40 neutralizing antibody partially restored CSA of the gastrocnemius (640.1 µm2 ± 59.83 of DSS + PBS vs. 1062.0 µm2 ± 83.41 of DSS + p40Ab, P < 0.0001) and tibialis anterior (678.9 µm2 ± 67.59 of DSS + PBS vs. 1105.3 µm2 ± 143.15 of DSS + p40Ab, P = 0.0003).vs. 640.1 µm2  ± 59.83 of DSS + PBS, P < 0.0001) and tibialis anterior (1251.8 µm2  ± 331.48 of cont. vs. 678.9 µm2  ± 67.59 of DSS + PBS, P < 0.0001), and the treatment of IL-12/23 p40 neutralizing antibody partially restored CSA of the gastrocnemius (640.1 µm2  ± 59.83 of DSS + PBS vs. 1062.0 µm2  ± 83.41 of DSS + p40Ab, P < 0.0001) and tibialis anterior (678.9 µm2  ± 67.59 of DSS + PBS vs. 1105.3 µm2  ± 143.15 of DSS + p40Ab, P = 0.0003). In the evaluation of muscle function, grip strength and fatigue distance decreased by colitis were partially restored (grip strength: 139.9 g ± 5.38 of cont. vs. 83.9 g ± 5.48 of DSS + PBS, P < 0.0001; DSS + PBS vs. 118.6 g ± 4.05 of DSS + p40Ab, P < 0.0001; fatigue distance: 872.5 m ± 104.01 of cont. vs. 58.2 m ± 107.72 of DSS + PBS, P < 0.0001; DSS + PBS vs. 328.0 m ± 109.71 of DSS + p40Ab, P = 0.0015) by injection of IL-12/23 p40 neutralizing antibody. CONCLUSIONS: Our study demonstrates that Il-12/23 acts directly on muscle to induce atrophy, and the IL-12/23 p40 neutralizing antibody is effective not only in suppressing colitis but also in maintaining muscle mass and improving muscle function in an experimental colitis model.

Relationship between DNA methylation changes and skeletal muscle mass.

BACKGROUND: Sarcopenia is a disease diagnosed in the elderly. In patients with sarcopenia, the muscle mass decreases every year. The occurrence of sarcopenia is greatly affected by extrinsic factors such as eating habits, exercise, and lifestyle. The present study aimed to determine the relationship between muscle mass traits and genes affected by epigenetic factors with three different adjustment methods using Korean Genome and Epidemiology Study (KOGES) data. RESULTS: We conducted a demographic study and DNA methylation profiling by three studies according to the muscle mass index (MMI) adjustment methods: appendicular skeletal muscle mass divided by body weight (MMI1); appendicular skeletal muscle mass divided by square of height (MMI2); appendicular skeletal muscle mass divided by BMI (MMI3). We analyzed differentially methylated regions (DMRs) for each group. We then restricted our subjects to be top 30% (T30) and bottom 30% (B30) based on each MMI adjustment method. Additionally, we performed enrichment analysis using PathfindR to evaluate the relationship between identified DMRs and sarcopenia. A total of 895 subjects were included in the demographic study. The values of BMI, waist, and hip showed a significant difference in all three groups. Among 446 participants, 44 subjects whose DNA methylation profiles were investigated were included for DNA methylation analysis. The results of enrichment analysis showed differences between groups. In the women group through MMI1 method, only the glutamatergic synapse pathway showed a significant result. In the men group through MMI2 method, the adherens junction pathway was the most significant. Women group through MMI2 method showed similar results, having an enriched Rap1 signaling pathway. In men group through MMI3 method, the Fc epsilon RI signaling pathway was the most enriched. Particularly, the notch signaling pathway was significantly enriched in women group through MMI3 method. CONCLUSION: This study presents results about which factor should be concerned first in muscle mass index (MMI) adjustment. The present study suggested that GAB2 and JPH3 in MMI1 method, HLA-DQB1 and TBCD in MMI2 method, GAB2, NDUFB4 and ISPD in MMI3 method are potential genes that can have an impact on muscle mass. It could enable future epigenetic studies of genes based on annotation results. The present study is a nationwide study in Korea with the largest size up to date that compares adjustment indices for MMI in epigenetic research.

Changes in aquaporins expression due to acute water restriction in naturally aging mice.

Aquaporins (AQPs) are water channels in the cell membrane that regulate osmosis in response to rapid changes in intracellular and extracellular fluid concentration caused by extrinsic factors. While there are so many studies on the association of AQPs with muscular atrophy, sarcopenia, and Duchenne muscular dystrophy (DMD), the expression of AQP has not been verified in naturally aging mice or humans. Notably, due to the characteristics of AQPs, the difference in function cannot be evaluated without extrinsic factors such as acute water restriction. The purpose of this study was to investigate the changes in AQPs expression and function due to natural aging under acute water restriction conditions in aging mice. The expression of AQP4 was shown to decrease with aging similar to previous studies. However, for the first time, this study results confirmed that AQP1 expression increased in aging mice. In addition, the expression of Aqp1 decreased in the acute water restricted group compared to the control group after acute water restriction in aging mice. These results suggest that although the expression of AQP1 increases with aging, its function is reduced. We also confirmed that overexpression of Aqp1 can inhibit myotube differentiation and that knockdown can promote myotube differentiation through in vitro experiments. In conclusion, based on our results, we suggest that the AQP1 is an important factor in sarcopenia caused by natural aging accompanied by chronic dehydration.

Alterations in gastric and gut microbiota following sleeve gastrectomy in high-fat diet-induced obese rats.

Obesity is considered a high-risk disease and a global epidemic, and the number of obese patients is rising at an alarming rate worldwide. High-fat diet-induced dysbiosis of the intestinal microbiota is considered an essential factor related to obesity. Bariatric surgery induces a sharp decrease in fat content and effectively improves the metabolism of obese individuals. Herein, we aimed to investigate the effects of a high-fat diet-induced obesity and the alterations in gastric and intestinal microbiota resulting from sleeve gastrectomy on clinical outcomes. We performed 16S sequencing of gastric and fecal samples obtained from rats in three treatment groups: normal chow diet, high-fat diet (HFD), and sleeve gastrectomy after HDF for 14 weeks. The area under the curve of fasting glucose and the levels of leptin and low-density lipoproteins were significantly different between groups. Microbial taxa that were highly correlated with several clinical parameters were identified for each group. Glyoxylate and dicarboxylate, taurine and hypotaurine, butanoate, nitrogen, and pyrimidine metabolism and aminoacyl-transfer ribonucleic acid biosynthesis were affected by bariatric surgery and were significantly associated with changes in the composition of gastric and fecal microbiomes. Connectivity and co-occurrence were higher in fecal samples than in gastric tissues. Our results elucidated the positive effects of sleeve gastrectomy in obesity and shed light on changes in the microbiomes of gastric and fecal samples.

Daily Walking Accompanied with Intermittent Resistance Exercise Prevents Osteosarcopenia: A Large Cohort Study.

BACKGROUND: This study aimed to analyze the effects of walking and resistance exercises on bone structure, bone mineral density (BMD), and skeletal muscle mass. We used data from the fourth Korean National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,477 participants aged ≥19 years underwent hip structural analysis (HSA), BMD, and skeletal muscle index (SMI). All radiologic evaluations were performed using dual energy X-ray absorptiometry (DXA). The Korean short version of the International Physical Activity Questionnaire was used to measure physical activity status. The physical activity recommendations of the American College of Rheumatology Work Group Panel were used to evaluate the extent of activity. RESULTS: The BMD and SMI in the group in which walking activity was performed 5 days or more per week for at least 30 min per day were significantly higher than those in the group in which walking activity was not performed. HSA and SMI in the group in which resistance exercise was performed 2 days or more per week for at least 30 min per day were found to be significantly higher than those in the group in which strengthening exercises were not performed. CONCLUSIONS: If resistance exercise and walking are combined, bone loss and muscle loss are prevented maintaining cortical thickness in the elderly. Walking for more than 5 days a week and resistance exercise for more than 2 days a week will help to maintain the skeletal muscle as well as the cortex around the femur neck, thus helping to prevent fragility fractures in older individuals.

Effects of lifelong spontaneous exercise on skeletal muscle and angiogenesis in super-aged mice.

There has been an increasing awareness of sarcopenia, which is characterized by a concomitant decrease in skeletal muscle mass and quality due to aging. Resistance exercise is considered more effective than aerobic exercise in terms of therapeutic exercise. To confirm the effect of long-term aerobic exercise in preventing sarcopenia, we evaluated the skeletal muscle mass, quality, and angiogenic capacity of super-aged mice that had undergone lifelong spontaneous exercise (LSE) through various experiments. Our findings show that LSE could maintain skeletal muscle mass, quality, and fitness levels in super-aged mice. In addition, ex vivo experiments showed that the angiogenic capacity was maintained at a high level. However, these results were not consistent with the related changes in the expression of genes and/or proteins involved in protein synthesis or angiogenesis. Based on the results of previous studies, it seems certain that the expression at the molecular level does not represent the phenotypes of skeletal muscle and angiogenesis. This is because aging and long-term exercise are variables that can affect both protein synthesis and the expression patterns of angiogenesis-related genes and proteins. Therefore, in aging and exercise-related research, various physical fitness and angiogenesis variables and phenotypes should be analyzed. In conclusion, LSE appears to maintain the potential of angiogenesis and slow the aging process to maintain skeletal muscle mass and quality. Aerobic exercise may thus be effective for the prevention of sarcopenia.

Differential gene expression profile by RNA sequencing study of elderly osteoporotic hip fracture patients with sarcopenia.

BACKGROUND: The purpose of this study was to report the RNA sequencing profile according to the presence or absence of sarcopenia in elderly patients with osteoporotic hip fracture. Therefore, an important genetic factor candidate for sarcopenia causing hip fracture in elderly with osteoporosis has been identified. METHODS: The patient group involved subjects over 65 years who had undergone hip fracture surgery. Among 323 hip fracture (HF) patients identified from May 2017 to December 2019, 162 HF patients (90 non-sarcopenia and 72 sarcopenia groups), excluding subjects with high energy trauma and non-osteoporosis, were finally included in the analysis. For RNA sequencing, each patient with hand grip strength (HGS) values in the top 10% were enrolled in the control group and with the bottom 10% in the patient group. After excluding patients with poor tissue quality, 6 patients and 5 patients were selected for sarcopenia and non-sarcopenia groups, respectively. For qPCR validation, each patient with HGS values in the top 20% and bottom 20% was enrolled in the control and patient groups, respectively. After excluding patients with poor tissue quality, 12 patients and 12 patients were enrolled in the sarcopenia and non-sarcopenia groups, respectively. Sarcopenia was defined according to the Asia Working Group for Sarcopenia (AWGS) criteria for low muscle strength (hand grip strength below 18 â€‹kg in women and 28 â€‹kg in men) and low muscle mass (SMI below 5.4 â€‹kg/m2 in women and 7.0 â€‹kg/m2 in men). The libraries were prepared for 100 bp paired-end sequencing using TruSeq Stranded mRNA Sample Preparation Kit (Illumina, CA, USA). The gene expression counts were supplied to Deseq2 to extract possible gene sets as differentially expressed genes (DEG) that discriminate between sarcopenia and non-sarcopenia groups that were carefully assigned by clinical observation. For the classification of the candidate genes from DEG analysis, we used the public databases; gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Quantitative real-time PCR was performed for validation. RESULTS: Samples collected were subjected to RNAseq using the Illumina platform. A total of 11 samples from both sarcopenia and non-sarcopenia groups were sequenced. Fifteen genes (RUNX 1, NGFR, CH3L1, BCL3, PLA2G2A, MYBPH, TEP1, SEMA6B, CSPG4, ACSL5, SLC25A3, NDUFB5, CYC1, ACAT1, and TCAP) were identified as differentially expressed genes (DEG) in both the groups.In the qPCR results, the expression levels of SLC25A3 and TCAP gene in the OS group were significantly lower than in the non-OS groups whereas an increase in RUNX1 mRNA level was observed in the OS samples (p â€‹< â€‹0.05). CONCLUSIONS: In summary, this study detected gene expression difference according to the presence or absence of sarcopenia in elderly osteoporosis female patients with hip fracture. We have also identified 15 important genes (RUNX 1, NGFR, CH3L1, BCL3, PLA2G2A, MYBPH, TEP1, SEMA6B, CSPG4, ACSL5, SLC25A3, NDUFB5, CYC1, ACAT1, TCAP), a few GO categories and biological pathways that may be associated with the osteosarcopenia. Our study may provide effective means for the prevention, diagnosis and treatment sarcopenia in elderly osteoporosis female patients. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: These findings provide a novel insight into the effects of aging on the response in women with postmenopausal osteoporosis. Further studies are underway to identify the specific signalling pathways involved. These results reveal potential therapeutic targets that could aid the regenerative capacity of aging skeletal muscle.

Draft genome of Semisulcospira libertina, a species of freshwater snail.

Semisulcospira libertina, a species of freshwater snail, is widespread in East Asia. It is important as a food source. Additionally, it is a vector of clonorchiasis, paragonimiasis, metagonimiasis, and other parasites. Although S. libertina has ecological, commercial, and clinical importance, its whole-genome has not been reported yet. Here, we revealed the genome of S. libertina through de novo assembly. We assembled the whole-genome of S. libertina and determined its transcriptome for the first time using Illumina NovaSeq 6000 platform. According to the k-mer analysis, the genome size of S. libertina was estimated to be 3.04 Gb. Using RepeatMasker, a total of 53.68% of repeats were identified in the genome assembly. Genome data of S. libertina reported in this study will be useful for identification and conservation of S. libertina in East Asia.

Two Types of Mouse Models for Sarcopenia Research: Senescence Acceleration and Genetic Modification Models.

Sarcopenia leads to loss of skeletal muscle mass, quality, and strength due to aging; it was recently given a disease code (International Classification of Diseases, Tenth Revision, Clinical Modification, M62.84). As a result, in recent years, sarcopenia-related research has increased. In addition, various studies seeking to prevent and treat sarcopenia by identifying the various mechanisms related to the reduction of skeletal muscle properties have been conducted. Previous studies have identified muscle synthesis and breakdown; investigating them has generated evidence for preventing and treating sarcopenia. Mouse models are still the most useful ones for determining mechanisms underlying sarcopenia through correlations and interventions involving specific genes and their phenotypes. Mouse models used to study sarcopenia often induce muscle atrophy by hindlimb unloading, denervation, or immobilization. Though it is less frequently used, the senescence-accelerated mouse can also be useful for sarcopenia research. Herein, we discuss cases where senescence-accelerated and genetically engineered mouse models were used in sarcopenia research and different perspectives to use them.

Trichinella spiralis infection ameliorated diet-induced obesity model in mice.

Obesity is an increasingly prevalent disease worldwide, and genetic and environmental factors are known to regulate the development of obesity and associated metabolic diseases. Emerging studies indicate that innate and adaptive immune cell responses in adipose tissue play critical roles in the regulation of metabolic homeostasis. Parasitic helminths are the strongest natural inducers of type 2 inflammatory responses, and several studies have revealed that helminth infections inversely correlate with metabolic syndrome. Hence, this study investigated whether helminth infections could have preventative effects on high fat diet-induced obesity. Female C57BL/6 mice were maintained on either a low fat diet (LFD, 10% fat) or a high fat diet (HFD, 60% fat) for 6 weeks after Trichinella spiralis infection. The mice were randomly divided into four groups and were fed a normal diet, LFD, LFD after T. spiralis infection (Inf + LFD), a high fat diet (HFD), or HFD after T. spiralis infection (HFD + inf). All groups were assayed for body weight, food efficiency ratio (FER), total body weight gain (g)/total food intake amount (g) fat weight, and blood biochemical parameters. Our data indicate that the HFD + inf group significantly reduced body weight gain, fat mass, total cholesterol, and FER. Analysis of immune cell composition by flow cytometry revealed that T. spiralis promoted strong decreases in proinflammatory adipose macrophages (F4/80+CD11c+) and T cells. The alterations in microbiota from fecal samples of mice were analyzed, which showed that T. spiralis infection decreased the ratio of Firmicutes to Bacteriodetes, thereby restoring the previously increased ratio of Firmicutes to Bacteriodetes in HFD-fed mice. Moreover, elimination of T. spiralis retained the protective effects in the HFD-fed obese mice whereas flubendazole (FLBZ) treatment increased levels of the families Lachnospiraceae and Ruminococcaceae. In summary, we provided novel data suggesting that helminth infection protects against obesity and the protection was closely related to M2 macrophage proliferation, an inhibiting proinflammatory response. In addition, it alters the microbiota in the gut.

Regular moderate aerobic exercise improves high-fat diet-induced nonalcoholic fatty liver disease via monoacylglycerol O-acyltransferase 1 pathway suppression.

PURPOSE: Monoacylglycerol O-acyltransferase 1 (MGAT1) is reported to play a key role in the development of diet-induced nonalcoholic fatty liver disease (NAFLD). Thus, this study investigated the effect of exercise on suppression of the MGAT1 pathway in NAFLD tissue of high-fat diet (HFD)-induced obese rats. METHODS: Male Sprague-Dawley rats were fed an HFD containing 45% fat for 6 weeks. Upon confirmation that NAFLD had been induced in the obese animals, they were divided into HFD-fed groups provided with exercise (HFD + EXE) or without exercise (HFD) and a group given dietary adjustment (DA) only, for a further 6 weeks of intervention treatment. The 6-week regular moderate aerobic exercise consisted of an accommodation phase with increasing exercise. Lipid accumulation in the liver tissue was determined by Oil Red O staining. The MGAT1 and liver lipogenic gene mRNA levels were measured by qPCR, and their protein levels by western blot assay. RESULTS: Oil Red O staining showed that NAFLD was successfully induced by HFD-fed. The gene expression of MGAT1 was significantly lower in HFD + EXE than HFD. However, there was no significant difference between HFD + EXE and DA. The protein expression of MGAT1 was significantly lower in HFD + EXE than both HFD and DA. Messenger RNA and protein expression of other lipogenic genes were not different among groups. These data indicate that exercise suppresses MGAT1 pathway regardless of HFD feeding; in part, this effect could be greater than DA. CONCLUSION: Our data suggest that exercise can improve NAFLD, which is probably due to suppression of MGAT1 pathway.