Similar Datasets
Project description:Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority are located in non-coding DNA regions. This suggests that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism.
| S-EPMC7264154 | biostudies-literature
Project description:Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors, and characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority is located in non-coding DNA regions. This suggest that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism and linked to SNPs associated with the development of obesity and T2D.
2020-03-26 | GSE126101 | GEO
Project description:Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors, and characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority is located in non-coding DNA regions. This suggest that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism and linked to SNPs associated with the development of obesity and T2D.
2020-03-26 | GSE126100 | GEO
Project description:Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors, and characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority is located in non-coding DNA regions. This suggest that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population. Thus, our combined genomic investigations identified genes that are involved in skeletal muscle metabolism and linked to SNPs associated with the development of obesity and T2D.
2020-03-26 | GSE126099 | GEO
Project description:Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans
| PRJNA521021 | ENA
Project description:Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans [ChIP-seq]
| PRJNA521022 | ENA
Project description:Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans [RNA-seq]
| PRJNA521024 | ENA
Project description:Skeletal muscle enhancer interactions identify genes controlling whole body metabolism in humans [cHiC-seq]
| PRJNA521025 | ENA
Project description:Iron deficiency impairs skeletal muscle metabolism. The underlying mechanisms are incompletely characterised, but animal and human experiments suggest the involvement of signalling pathways co-dependent upon oxygen and iron availability, including the pathway associated with hypoxia-inducible factor (HIF). We performed a prospective, case-control, clinical physiology study to explore the effects of iron deficiency on human metabolism, using exercise as a stressor. Thirteen iron-deficient (ID) individuals and thirteen iron-replete (IR) control participants each underwent 31P-magnetic resonance spectroscopy of exercising calf muscle to investigate differences in oxidative phosphorylation, followed by whole-body cardiopulmonary exercise testing. Thereafter, individuals were given an intravenous (IV) infusion, randomised to either iron or saline, and the assessments repeated ~ 1 week later. Neither baseline iron status nor IV iron significantly influenced high-energy phosphate metabolism. During submaximal cardiopulmonary exercise, the rate of decline in blood lactate concentration was diminished in the ID group (P = 0.005). Intravenous iron corrected this abnormality. Furthermore, IV iron increased lactate threshold during maximal cardiopulmonary exercise by ~ 10%, regardless of baseline iron status. These findings demonstrate abnormal whole-body energy metabolism in iron-deficient but otherwise healthy humans. Iron deficiency promotes a more glycolytic phenotype without having a detectable effect on mitochondrial bioenergetics.
| S-EPMC8770476 | biostudies-literature
Project description:This study identified the changes in hypertrophy/atrophy and mitochondrial-related signaling in human skeletal muscle following whole-body (WB) and localized single leg (SL) heat treatment. Nine active male participants were administered either 60 min of passive WB (44-50°C, 50% humidity) or SL (water-perfused suit at 49.5 ± 1.4°C) heat treatment at least 1 week apart in a counterbalanced order. The untreated leg during SL was considered as control (CON). Core, skin, and quadriceps muscle temperature were monitored throughout the experimental trials. Muscle microbiopsy samples were obtained prior to (PRE), and 30 min and 3 h post (POST) following heat treatment. Muscle temperature increased with time (p < 0.0001) in both WB and SL, with no differences between conditions (38.8 ± 0.5°C vs. 38.1 ± 0.6°C, p = 0.065). Core temperature increased only following WB, and was significantly higher compared with SL (39.1 ± 0.3°C vs. 37.1 ± 0.1, p < 0.0001). Compared with PRE, WB up-regulated the phosphorylation status of the majority of the Akt/mTOR pathway (Akt, mTOR, S6K1, rpS6, and p-eIF4E; p ≤ 0.050), with the exception of 4EBP1 (p = 0.139). WB also increased the mRNA of HSPs 72, 90, and 25 (all p < 0.021), and increased or tended to increase the phosphorylation of FOXO1 (p = 0.066) and FOXO3a (p = 0.038). In addition, most (NRF1, NRF2, COX2, and COX4-I2; all p ≤ 0.050), but not all (CS, Cyt c, and COX4-I1; p > 0.441) mRNA content indicative of mitochondrial biogenesis were increased following WB, with no changes evident in these parameters in SL or CON (all p > 0.090). These results indicate that 1 h of WB heat treatment enhanced anabolic (Akt/mTOR), mitochondrial, and cyto-protective signaling (HSP), with a concomitant possible inhibition of FOXO transcription factors.
| S-EPMC7381176 | biostudies-literature