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- All Subjects: Obesity
- All Subjects: COVID-19
- Creators: Katsanos, Christos
Polarography was used to determine functional differences in isolated SS and IMF mitochondria between lean (37 ± 3 yrs; n = 10) and obese (35 ± 3 yrs; n = 11) subjects during either saline (control) or amino acid (AA) infusions. AA infusion increased ADP-stimulated respiration (i.e., coupled respiration), non-ADP stimulated respiration (i.e., uncoupled respiration), and ATP production rates in SS, but not IMF mitochondria in lean (n = 10; P < 0.05). Neither infusion increased any of the above parameters in muscle SS or IMF mitochondria of the obese subjects.
Using label free quantitative mass spectrometry, we determined differences in proteomes of SM SS and IMF mitochondria between lean (33 ± 3 yrs; n = 16) and obese (32 ± 3 yrs; n = 17) subjects. Differentially-expressed mitochondrial proteins in SS versus IMF mitochondria of obese subjects were associated with biological processes that regulate: electron transport chain (P<0.0001), citric acid cycle (P<0.0001), oxidative phosphorylation (P<0.001), branched-chain amino acid degradation, (P<0.0001), and fatty acid degradation (P<0.001). Overall, these findings show that obesity is associated with redistribution of key biological processes within the mitochondrial reticulum responsible for regulating energy metabolism in human skeletal muscle.
Subjects and Methods: Forty-five sedentary overweight and obese adult participants with a waist circumference greater than 32 inches for women and 37 inches for men were randomly assigned to one of two groups, the vinegar group (VIN, n=21) or the control group (CON, n=24), and instructed to consume either two tablespoons of liquid red wine vinegar (3.6g acetic acid) or a control pill (0.0225g acetic acid) twice daily at the beginning of a meal for 8 weeks. Participants were also instructed to maintain normal diet and physical activity levels. Anthropometric measures, dual-energy x-ray absorptiometry (DXA) scans, blood samples, and 24-hour dietary recalls were collected at baseline and at end of trial. A compliance calendar was provided for daily tracking of vinegar supplementation.
Results: Compliance to vinegar supplementation averaged 92.7 ±13.3% among the VIN group and 89.1 ±18.9% among the CON group. There were no statistically significant differences in anthropometric measurements between baseline and week 8: weight (P=0.694), BMI (P=0.879), and waist circumference (P=0.871). Similarly, DXA scan data did not show significant changes in visceral fat (P=0.339) or total fat (P=0.294) between baseline and week 8. The VIN group had significant reductions in fasting glucose (P=0.003), fasting insulin (P <0.001), and homeostatic model assessment of insulin resistance scores (P <0.001) after treatment.
Conclusions: These data do not support the findings from previous studies that indicated a link between vinegar supplementation and increased fat metabolism, specifically visceral fat reduction.
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.
Vaccines are modern medicine’s best way of combating the majority of viral and bacterial illnesses and contagions to date. Thanks to the introduction of vaccines since the first uses of them in 1796 (Jenner’s smallpox vaccine), they have drastically reduced figures of disease worldwide, turning once lethal and life changing conditions into minor annoyances; Some of these afflictions have even become nonexistent or even extinct in certain parts of the world outside of a controlled laboratory setting. With many advancements and overwhelming evidence proving their efficiency, it is clear that vaccines have become nothing less than a necessity for everyday healthcare in today’s world. <br/>The greatest contributor to the creation and evolution of vaccines throughout the years is by far the progress and work done in the field of molecular and cellular biology. These advancements have become the bedrock of modern vaccination, as shown by the differing types of vaccines and their methodology. The most common varieties of vaccines are include ‘dead’ or inactivated vaccines, one such example being the pertussis strain of vaccines, which have either dead or torn apart cells for the body to easily fight off, allowing the immune system to easily and quickly counter the illness; Additionally, there are also live attenuated vaccines (LAVs) in which a weaker version of the pathogen is introduced to the body to stimulate an immune response, or a recombinant mRNA vaccine where mRNA containing the coding for an antigen is presented for immunological response, the latter being what the current COVID-19 vaccines are based on. This is in part aided by the presence of immunological adjuvants, antigens and substances that the immune system can recognize, target, and remember for future infections. However, for more serious illnesses the body needs a bigger threat to analyze, which leads to live vaccines- instead of dead or individual components of a potential pathogen, a weakened version is created in the lab to allow the body to combat it. The idea behind this is the same, but to a larger degree so a more serious illness such as measles, mumps, and rubella (MMR) do not infect us.<br/>However, for the past couple of decades the public’s views on vaccination has greatly varied, with the rise of fear and disinformation leading those to believe that modern medicine is a threat in disguise. The largest of these arguments began in the late 90’s, when Dr. Andrew Wakefield published an article under the Lancet with false information connecting vaccinations to the occurrence of autism in younger children- a theory which has since then been proven incorrect numerous times over. Unfortunately, the rise of hysteria and paranoia in people, along with more misinformation from misleading sources, have strengthened the anti-vaccination cause and has made it into a serious threat to the health of those world-wide.<br/>The aim of this thesis is to provide an accurate and thorough analysis on these three themes- the history of vaccines, their inner workings and machinations in providing immune defenses for the body, and the current controversy of the anti-vaccination movement. Additionally, there will be two other sections going in-depth on two specific areas where vaccination is highly important; The spread and fear of the Human Immunodeficiency Virus (HIV) has been around for nearly four decades, so it begs the question: what makes this such a difficult virus, and how can a vaccine be created to combat it? Additionally, in the last year the world has encountered a new virus that has evolved into a global pandemic, SARS-COV 2. This new strain of coronavirus has shown itself to be highly contagious and rapidly mutating, and the race to quickly develop a vaccine to counteract it has been on-going since its first major infections in Wuhan, China. Overall, this thesis will go in-depth in providing the most accurate, up-to-date, and critical information regarding vaccinations today.