Filtering by
- All Subjects: Exercise
- All Subjects: Insulin Resistance
- Creators: Katsanos, Christos
Assessment of DNA methylation was performed on human skeletal muscle and blood using reduced representation bisulfite sequencing (RRBS) for high-throughput identification and pyrosequencing for site-specific confirmation. Sorbin and SH3 homology domain 3 (SORBS3) was identified in skeletal muscle to be increased in methylation (+5.0 to +24.4 %) in the promoter and 5’untranslated region (UTR) in the obese participants (n= 10) compared to lean (n=12), and this finding corresponded with a decrease in gene expression (fold change: -1.9, P=0.0001). Furthermore, SORBS3 was demonstrated in a separate cohort of morbidly obese participants (n=7) undergoing weight-loss induced by surgery, to decrease in methylation (-5.6 to -24.2%) and increase in gene expression (fold change: +1.7; P=0.05) post-surgery. Moreover, SORBS3 promoter methylation was demonstrated in vitro to inhibit transcriptional activity (P=0.000003). The methylation and transcriptional changes for SORBS3 were significantly (P≤0.05) correlated with obesity measures and fasting insulin levels. SORBS3 was not identified in the blood methylation analysis of lean (n=10) and obese (n=10) participants suggesting that it is a muscle specific marker. However, solute carrier family 19 member 1 (SLC19A1) was identified in blood and skeletal muscle to have decreased 5’UTR methylation in obese participants, and this was significantly (P≤0.05) predicted by insulin sensitivity.
These findings suggest SLC19A1 as a potential blood-based biomarker for obese, insulin resistant states. The collective findings of SORBS3 DNA methylation and gene expression present an exciting novel target in skeletal muscle for further understanding obesity and its underlying insulin resistance. Moreover, the dynamic changes to SORBS3 in response to metabolic improvements and weight-loss induced by surgery.
Seven human subjects with body mass indices (BMIs) ranging from 19.4 kg/ m2 to 26.7 kg/ m2 and six human subjects with BMIs ranging from 32.1 kg/ m2 to 37.6 kg/ m2 were recruited and subjected to 45-minute bouts of acute exercise to look at the changes in the plasma concentration of the dopamine metabolite homovanillic acid (HVA) in response to acute physical activity. Plasma HVA concentration was measured before exercise and during the last 10 minutes of the exercise bout via competitive ELISA. On average the optical density (OD) of the samples taken from lean subjects decreased from 0.203 before exercise to 0.192 during exercise, indicating increased plasma HVA concentration. In subjects with obesity OD increased from 0.210 before exercise to 0.219 during exercise, indicating reduced plasma HVA concentration. These differences in OD were not statistically significant. Between the lean group and the group with obesity no significant difference was observed between the OD of the plasma samples taken before exercise, but a significant difference (p = 0.0209) was observed between the ODs of the samples taken after exercise. This indicated that there was a significant difference between the percent changes in OD between the lean group and the group with obesity, which suggested that there may be a body weight-dependent difference in the amount of dopamine released in response to exercise. Because of the lack of significance in the changes in OD within the lean group and the group with obesity the results of this study were insufficient to conclude that this difference is not due to chance, but further investigation is warranted.
In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise over time.
In this quantitative research paper, we explored the correlation between the six dimensions of motivation as part of the Self-Determination Theory spectrum and physical activity. In addition, our aim was to also see if Transcranial Direct Current Stimulation (tDCS) paired with exercise as an intervention would affect motivation to exercise over time.
A total of 26 human subjects were used in this study. Each subject was classified as either lean or obese, according to their BMI measurement. First, the subjects underwent an oral glucose tolerance test. Blood samples were taken to measure glucose levels in the blood. After the test subject characteristics for each subject was obtained. These included age, BMI, body fat percentage, fat free mass (FFM), height, total mass, waist circumference, hip circumference, and waist to hip ratio. After the subject characteristics and blood glucose were measured the blood samples taken previously were then centrifuged, and the blood plasma was extracted. The blood plasma was then used to undergo an Insulin ELISA test. After extensive analysis, the Matsuda Index of each subject was obtained. Subjects with a Matsuda value of 6.0 or under were considered insulin resistant while subjects with a Matsuda value higher than 6.0 were considered insulin sensitive. Subjects were also required to submit a dietary record over the course of three days. The food intake was then put into a food processing software which gave a daily average of the macro and micro nutrients for each subject. Both the subject and dietary values were put into a multiple regression with a significance factor of p < 0.5 to see which factors contributed most to the Matsuda value.
It was found that BMI, height, total mass, insulin and fat free mass, all of which were subject characteristics, were considered to be significant. Some of these factors an individual has no control over, such as height and insulin. However other factors such as BMI, total mass and fat free mass can be affected by both a healthy diet and frequent exercise. This study validated that diet and physical activity can greatly influence an individual’s susceptibility to insulin resistance and ultimately T2DM.
According to the CDC, obesity has increased from 30.5% to 42.4% over the past 18 years. Western diets (WDs) consist of large portions in high fats, high carbohydrates, excess sugar and high-glycemic foods that can cause metabolic complications and mitochondrial dysfunction. Diet-induced obesity can lead to changes in muscle metabolism and muscle fiber phenotypes, which in turn lead to metabolic complications. Muscle fiber phenotype is determined protein isoform-content of myosin heavy chain (MHC). Regular exercise alters mitochondrial content and fat oxidation and shifts MHC proportions under healthy circumstances. However, diet and exercise-driven fiber type shifts in diet-induced obesity are less understood. We designed our experiment to better understand the impact of diet and/ or exercise on fiber type content of gastrocnemius muscle in diet-induced obese mice. Exercise and genistein may be used as a treatment strategy to restore the MHC proportions in obese subjects to that of the lean subjects. We hypothesized that genistein and exercise would have the greatest MHC I change in muscle fiber phenotype of mouse gastrocnemius muscles. Further, we also hypothesized that a standard diet would reverse the expected increase in fast fiber phenotype (MHC IIb). Lastly, we also hypothesized that exercise would also reduce the abundance of MHC IIb. Gastrocnemius muscles were collected from mice, homogenized, run through gel electrophoresis and stained to give muscle fiber proportions. Paired sample t-tests were conducted for differences between the MHC isoforms compared to the lean (LN) and high-fat diet (HFD) control groups. The results showed that genistein and exercise significantly increased the abundance of MHC I muscle fibers (19%, p<0.05). Additionally, diet and exercise restored the muscle fiber phenotype to that of lean control. As expected, HFD obese mice exhibited elevated fast twitch fibers compared to only 3% slow twitch fibers. These findings show the potential for exercise and supplementation of genistein as a strategy to combat diet induced obesity. Future research should aim to understand the mechanisms that genistein acts on to make these changes, and aim to replicate these data in humans with obesity.
