Human skeletal muscle methylome after low carbohydrate energy balanced exercise
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PROVIDER: PRJNA928381 | ENA |
REPOSITORIES: ENA
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Project description:We aimed to investigate the human skeletal muscle (SkM) DNA methylome after exercise in low carbohydrate (CHO) energy balance (with high fat) compared with exercise in low-CHO energy deficit (with low fat) conditions. The objective to identify novel epigenetically regulated genes and pathways associated with ‘train-low sleep-low’ paradigms. The sleep-low conditions included 9 males that cycled to deplete muscle glycogen while reaching a set energy expenditure. Post-exercise, low-CHO meals (protein-matched) completely replaced (using high-fat) or only partially replaced (low-fat) the energy expended. The following morning resting baseline biopsies were taken and the participants then undertook 75 minutes of cycling exercise, with skeletal muscle biopsies collected 30 minutes and 3.5 hours post exercise. Discovery of genome-wide DNA methylation was undertaken using Illumina EPIC arrays and targeted gene expression analysis was conducted by RT-qPCR. At baseline participants under energy balance (high fat) demonstrated a predominantly hypermethylated (60%) profile across the genome compared to energy deficit-low fat conditions. However, post exercise performed in energy balance (with high fat) elicited a more prominent hypomethylation signature 30 minutes post-exercise in gene regulatory regions important for transcription (CpG islands within promoter regions) compared with exercise in energy deficit (with low fat) conditions. Such hypomethylation was enriched within pathways related to: IL6-JAK-STAT signalling, metabolic processes, p53 / cell cycle and oxidative / fatty acid metabolism. Hypomethylation within the promoter regions of genes: HDAC2, MECR, IGF2 and c13orf16 were associated with significant increases in gene expression in the post-exercise period in energy balance compared with energy deficit. Furthermore, histone deacetylase, HDAC11 was oppositely regulated at the gene expression level compared with HDAC2, where HDAC11 was hypomethylated yet increased in energy deficit compared with energy balance conditions. Overall, we identify some novel epigenetically regulated genes associated with train-low sleep-low paradigms.
2023-03-29 | GSE223786 | GEO
Project description:The methylome and transcriptome signatures following exercise that are physiologically and metabolically relevant to sporting contexts such as team sports or health prescription scenarios (e.g. high intensity interval training/HIIT) has not been investigated. To explore this, we performed two different sport/exercise relevant high-intensity running protocols in 5 male sport team members using a repeated measures design of: 1) Change of direction (COD) versus; 2) straight line (ST) exercise with a wash-out period of at least 2 weeks between trials. Skeletal muscle biopsies collected from the vastus lateralis 30 minutes and 24 hours post exercise, were assayed using 850K methylation arrays and a comparative analysis with recent (subject-unmatched) sprint and acute aerobic exercise meta-analysis transcriptomes was performed. Despite COD and ST exercise being matched for classically defined intensity measures (speed x distance and number of accelerations/decelerations), COD exercise elicited greater movement (GPS-Playerload), physiological (HR), metabolic (lactate) as well as central and peripheral (differential RPE) measures compared with ST exercise, suggesting COD exercise evoked a higher exercise intensity. The exercise response alone across both conditions evoked extensive alterations in the methylome 30 mins and 24 hrs post exercise, particularly in MAPK, AMPK and axon guidance pathways. COD evoked a considerably greater hypomethylated signature across the genome compared with ST exercise, particularly at 30 minutes post exercise, enriched in: Protein binding, MAPK, AMPK, insulin, and axon guidance pathways. Comparative methylome analysis with sprint running transcriptomes identified considerable overlap, with 49% of genes that were altered at the expression level also differentially methylated after COD exercise. After differential methylated region analysis, we observed that VEGFA and its downstream nuclear transcription factor, NR4A1 had enriched hypomethylation within their promoter regions. VEGFA and NR4A1 were also significantly upregulated in the sprint transcriptome and meta-analysis of exercise transcriptomes. We confirmed increased gene expression of VEGFA, and considerably larger increases in the expression of canonical metabolic genes, PPARGC1A (that encodes PGC1-α) and NR4A3 in COD vs. ST exercise. Overall, we demonstrate that increased physiological/metabolic load via change of direction exercise in human skeletal muscle evokes considerable epigenetic modifications that are associated with changes in expression of genes responsible for adaptation to exercise.
2021-01-21 | GSE162288 | GEO
Project description:Adipose Energy Homeostasis is the important guarantee to maintain the body's energy balance. Recently, it is reported that, in the adipose cell, Kisspeptins play important role in cell proliferation, differentiation, lipid metabolism and some adipocytokine secretion, so Kisspeptins maybe the novel targets of adipose energy homeostasis regulation. Adipose tissue is the core organs that regulates adipose energy homeostasis. Our early studies observed that there is organizational difference that exercise regulated adipose energy homeostasis, and the response of the Kisspeptins to exercise is closely related to the energy state of the body, so we speculated that Kisspeptins play some important role in the exercise regulated adipose energy homeostasis. Based on the cell experiments to clarify the role of Kisspeptins in regulating adipose energy homeostasis, the role of Kisspeptins in the regulation of adipose energy homeostasis were determined in the adipose tissue of conditioned Kiss1 gene knockout mice of CRISPR/Cas9, then we use the single cell transcriptome sequencing, untargeted proteome and targeted metabolome techniques to further explore and elucidate the possible pathways and mechanisms of Kisspeptins mediated adipose energy homeostasis regulated by exercise.
2024-04-22 | PXD051630 |
Project description:Fast food diet consumption and sedentary life style leads to energy excess, which elevates risks for obesity, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and cancer. Exercise training conveys many health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms globally and at select loci in an array of human tissues, however, such effects are less well documented in liver tissue. To dissect the epigenetic consequences of diet and exercise in liver, we measured DNA methylation using reduced representation bisulfite sequencing (RRBS) and transcriptome using RNA-seq in mice maintained on a fast food diet with sedentary lifestyle (FFC) or exercise (FFE) compared to control diet with (NCE) and without exercise (NCC). Our analyses demonstrate genome-wide differential DNA methylation at key regulatory regions, including different classes of promoters and enhancers, and differential regulation of gene clusters in each condition group. FFE gene expression is most differentially regulated, with enrichment of carbohydrate/lipid metabolic pathways and skeletal muscle development in altered gene sets. Through evaluation of putative protective effects of exercise on diet-induced DNA methylation and gene expression, we show that hypermethylation is effectively prevented, especially at promoters and enhancers, and hypomethylation is partially attenuated. We assessed diet-induced DNA methylation changes associated with cancer-related epigenetic modifications and identified significant increases at liver-specific enhancers in FFC and FFE, suggesting a repressive effect on the epigenomic signature specifying liver identity. Gaining methylation at a subset of gene promoters was associated with inhibition of tissue development and promotion of carcinogenic process. Taken together, our study demonstrates large-scale diet- and exercise-induced effects on the epigenetic landscape, emphasizing the functional relevance of epigenetic mechanisms as an interface between life-style modifications and phenotypic alterations.
2017-08-25 | GSE85772 | GEO
Project description:Skeletal muscle can undergo large transcriptional changes in response to environmental stimuli such as diet or exercise in order to adapt to energetic demands. This remodelling has been associated with changes in muscle DNA methylation potentially regulating gene transcription. Despite abundant evidence that environmental stimuli can alter muscle DNA methylation, the mechanisms by which DNA methylation machinery respond to these stimuli and whether these have a physiological impact is still unclear. Therefore, we decided to investigate the importance of de novo DNA methylation on muscle methylation and function. We generated muscle specific DNMT3a knockout mice (mDKO) and investigated the impact of ablating DNMT3a in muscle on muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3a reduced DNA methylation in muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation. However, mDKO mice had a similar exercise capacity and whole-body energy metabolism as WT mice. Similarly, loss of DNMT3a did not alter muscle mitochondrial function or the transcriptional response to exercise however did increase the expression of genes involved in muscle development. These data suggest that DNMT3a does not have a large role in the function of mature muscle although a role in muscle development and differentiation is still likely.
2021-01-25 | GSE152348 | GEO
Project description:Skeletal muscle can undergo large transcriptional changes in response to environmental stimuli such as diet or exercise in order to adapt to energetic demands. This remodelling has been associated with changes in muscle DNA methylation potentially regulating gene transcription. Despite abundant evidence that environmental stimuli can alter muscle DNA methylation, the mechanisms by which DNA methylation machinery respond to these stimuli and whether these have a physiological impact is still unclear. Therefore, we decided to investigate the importance of de novo DNA methylation on muscle methylation and function. We generated muscle specific DNMT3a knockout mice (mDKO) and investigated the impact of ablating DNMT3a in muscle on muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3a reduced DNA methylation in muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation. However, mDKO mice had a similar exercise capacity and whole-body energy metabolism as WT mice. Similarly, loss of DNMT3a did not alter muscle mitochondrial function or the transcriptional response to exercise however did increase the expression of genes involved in muscle development. These data suggest that DNMT3a does not have a large role in the function of mature muscle although a role in muscle development and differentiation is still likely.
2021-01-25 | GSE152347 | GEO
Project description:Acute physical exercise elicits changes in gene expression in skeletal muscles to promote metabolic changes and to repair exercise-induced muscle injuries. Here, we investigated the impact of a single bout of running exercise until exhaustion on global transcriptional profiles in porcine skeletal muscles. Using a combined microarray and candidate gene approach, we identified a suite of genes that are differentially expressed in muscles during post-exercise recovery. Thus, several members of the heat shock protein family and proteins associated with proteolytic events were significantly up-regulated, suggesting that protein breakdown, prevention of protein aggregation and stabilization of unfolded proteins are important processes for restoring cellular homeostasis. We also detected an up-regulation of genes, which have been reported to be associated with muscle cell proliferation and differentiation, possibly reflecting an activation, differentiation and fusion of satellite cells to facilitate repair of muscle damage. In addition, exercise increased expression of the nuclear hormone receptors, which regulates metabolic functions associated with lipid, carbohydrate and energy homeostasis. Finally, we observed an unanticipated involvement of long non-coding RNA transcripts, which have been implicated in RNA processing and nuclear retention of adenosine-to-inosine edited mRNAs. These findings expand the complexity of pathways affected by acute contractile activity of skeletal muscle, contributing to a better understanding of the molecular processes that occur in muscle tissue in the recovery phase. Gene expression study of the porcine muscle Biceps femoris in regard to exercise, pigs allowed to rest for 0 hours, 1 hour and 3 hours after exercise were compared with pigs that had not been exercising, using in-house printed porcine two-colour oligonucleotide microarrays.
2012-07-12 | E-GEOD-30013 | biostudies-arrayexpress
Project description:Acute physical exercise elicits changes in gene expression in skeletal muscles to promote metabolic changes and to repair exercise-induced muscle injuries. Here, we investigated the impact of a single bout of running exercise until exhaustion on global transcriptional profiles in porcine skeletal muscles. Using a combined microarray and candidate gene approach, we identified a suite of genes that are differentially expressed in muscles during post-exercise recovery. Thus, several members of the heat shock protein family and proteins associated with proteolytic events were significantly up-regulated, suggesting that protein breakdown, prevention of protein aggregation and stabilization of unfolded proteins are important processes for restoring cellular homeostasis. We also detected an up-regulation of genes, which have been reported to be associated with muscle cell proliferation and differentiation, possibly reflecting an activation, differentiation and fusion of satellite cells to facilitate repair of muscle damage. In addition, exercise increased expression of the nuclear hormone receptors, which regulates metabolic functions associated with lipid, carbohydrate and energy homeostasis. Finally, we observed an unanticipated involvement of long non-coding RNA transcripts, which have been implicated in RNA processing and nuclear retention of adenosine-to-inosine edited mRNAs. These findings expand the complexity of pathways affected by acute contractile activity of skeletal muscle, contributing to a better understanding of the molecular processes that occur in muscle tissue in the recovery phase. Gene expression study of the porcine muscle Longissimus dorsi in regard to exercise, pigs allowed to rest for 0 hours, 1 hour and 3 hours after exercise were compared with pigs that had not been exercising, using in-house printed porcine two-colour oligonucleotide microarrays.
2012-07-12 | E-GEOD-30014 | biostudies-arrayexpress
Project description:Exercise training is a potent treatment of NAFLD and hepatic insulin resistance. Here we provide molecular information about the hepatic mitochondrial metabolism in mice when chronic overnutrition (high-energy diet (HED) for 6 weeks) is combined with exercise training. Training reduced the hepatic triacylglycerol content, fasting insulin, and reversed glucose intolerance. Training modified the hepatic mitochondrial proteome with a decrease in enzymes related to pyruvate metabolism and entry of acetyl-CoA into the TCA cycle. Transcriptome data revealed down-regulation of glucose oxidation and lipogenesis. The mitochondrial respiratory capacity of trained HED-fed mice is increased despite reduced content of complex I. Training decreased diacylglycerol species and JNK phosphorylation, both of which can induce insulin resistance. Increased mitochondrial mass and oxidative capacity of the trained muscle further unburdens the liver from substrate overload. Together, when high fat and carbohydrate intake in mice is accompanied by exercise, the decline of mitochondrial function and insulin resistance can be prevented by modification of mitochondrial acetyl-CoA metabolism.
2021-10-15 | GSE167046 | GEO
Project description:The liver plays a central role in vertebrate glucose homeostasis, and is also one of the most sexually dimorphic organs in terms of gene expression. While the extent of hepatic sexual dimorphism has been well described in mammals, little is known regarding this phenomenon in non-mammalian species, particularly fish. In this study, we examined hepatic gene expression and physiological phenotypes (growth, proximate body composition, retention efficiencies) to determine whether male and female zebrafish respond differently to diets comprised of 0, 15, 25, or 35 % carbohydrate. Using both Affymetrix microarrays and qRTPCR, we observed substantial sexual dimorphism in the hepatic transcriptome, and the response of some genes to dietary carbohydrate manipulation also varied by sex. Males upregulated genes associated with oxidative metabolism, carbohydrate metabolism, energy production, and amelioration of oxidative stress, while females had higher expression levels of genes associated with translation. Males also expressed elevated levels of hnf4a, a gene thought to be involved in regulating hepatic sexual dimorphism in the rodent. Dietary carbohydrate affected hepatic gene expression, growth performance, retention efficiencies of protein and energy, and percentage of moisture, lipid, and ash. Significant diet effects reflected differences between the 0% carbohydrate diet and the other diets, consistent with previous work on other cyprinids showing a high tolerance for dietary carbohydrate. Our data support the use of the zebrafish as a model for the study of both normal and disease states associated with carbohydrate metabolism, and highlight the importance of accounting for both sex and diet Keywords: Nutritional manipulation, sex comparison
2008-03-31 | GSE8856 | GEO