Characterization of Muscle Fiber Types in Humans with Obesity

Description
Obesity is a complex metabolic condition characterized by excessive adipose tissue accumulation, often leading to adverse health outcomes such as insulin resistance, cardiovascular disease, and reduced physical function. This paper delves into the dynamic spectrum of muscle fiber types in

Obesity is a complex metabolic condition characterized by excessive adipose tissue accumulation, often leading to adverse health outcomes such as insulin resistance, cardiovascular disease, and reduced physical function. This paper delves into the dynamic spectrum of muscle fiber types in obesity, highlighting their continuum nature rather than rigid classifications. We explore how alterations in fiber distribution, particularly an increase in hybrid fibers and glycolytic types, are more prevalent in obese individuals.
Date Created
2024-05
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Transcranial Direct Current Stimulation Followed by Exercise as an Intervention to Increase Motivated Physical Activity Behavior in Healthy Participants

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Description
This dissertation research project developed as an urgent response to physical inactivity, which has resulted in increased rates of obesity, diabetes, and metabolic disease worldwide. Incorporating enough daily physical activity (PA) is challenging for most people. This research aims to

This dissertation research project developed as an urgent response to physical inactivity, which has resulted in increased rates of obesity, diabetes, and metabolic disease worldwide. Incorporating enough daily physical activity (PA) is challenging for most people. This research aims to modulate the brain's reward systems to increase motivation for PA and, thus, slow the rapid increase in sedentary lifestyles. Transcranial direct current stimulation (tDCS) involves brain neuromodulation by facilitating or inhibiting spontaneous neural activity. tDCS applied to the dorsolateral prefrontal cortex (DLPFC) increases dopamine release in the striatum, an area of the brain involved in the reward–motivation pathways. I propose that a repeated intervention, consisting of tDCS applied to the DLPFC followed by a short walking exercise stimulus, enhances motivation for PA and daily PA levels in healthy adults. Results showed that using tDCS followed by short-duration walking exercise may enhance daily PA levels in low-physically active participants but may not have similar effects on those with higher levels of daily PA. Moreover, there was a significant effect on increasing intrinsic motivation for PA in males, but there were no sex-related differences in PA. These effects were not observed during a 2-week follow-up period of the study after the intervention was discontinued. Further research is needed to confirm and continue exploring the effects of tDCS on motivation for PA in larger cohorts of sedentary populations. This novel research will lead to a cascade of new evidence-based technological applications that increase PA by employing approaches rooted in biology.
Date Created
2023
Agent

Understanding the Regulation of Endothelial-bound Lipoprotein Lipase Activity in Humans at Risk of Type 2 Diabetes and Cardiovascular Disease

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Description
Elevated triglycerides (TG) are a hallmark of insulin resistance, which is generally caused by lower lipoprotein lipase (LPL) activity in the vasculature. LPL hydrolyzes TGs into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose tissue,

Elevated triglycerides (TG) are a hallmark of insulin resistance, which is generally caused by lower lipoprotein lipase (LPL) activity in the vasculature. LPL hydrolyzes TGs into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with LPL to modulate its function, and by inhibiting or activating LPL, respectively. Therefore, these proteins play key role in plasma lipid metabolism, but their role in regulating LPL activity in human insulin resistant (IR) (i.e., pre-diabetic) state is not known. Thus, the purpose of this research was to evaluate the concentrations of ApoC3 and ApoC2 in plasma along with the endothelial-bound LPL availability and activity in IR humans and in healthy, insulin sensitive (IS)/control humans. Insulin resistance was evaluated from plasma insulin and glucose responses to an oral glucose tolerance test, and by calculating the Matsuda index. Subjects were placed in the following groups: IR subjects, Matsuda index <4.0 (N=7; 4 males, 3 females); IS, Matsuda index >7.0 (N=11, 9 males, 2 females). IR and IS subjects received an intravenous infusion of insulin (1 mU/kg/min and 0.5 mU/kg/min, respectively) for 30 minutes to stimulate LPL activity. Whole-body endothelial-bound LPL was released from the vasculature by intravenous infusion of heparin. Plasma samples were collected 10 minutes after heparin infusion and analyzed for LPL concentration and activity, and ApoC3 and ApoC2 concentrations. Although plasma LPL concentrations were not different between groups (IR = 457 ± 17 ng/ml, IS = 453 ± 27 ng/ml, P = 0.02), plasma LPL activity was higher in the IR subjects (IR = 665 ± 113 nmol/min/ml, IS = 365 ± 59 nmol/min/ml, P = 0.02). IR subjects had higher concentrations of plasma ApoC3 (IR = 3.6 ± 0.5 mg/dl, IS = 2.7 ± 0.2 mg/dl, P=0.03). However, ApoC2 concentration was not different between groups (IR = 0.15 ± 0.03 mg/dl, IS = 0.11 ± 0.01 mg/dl, P = 0.11). These findings suggest that circulating APOC3 and ApoC2 are not key determinants regulating LPL activity during hyperinsulinemia in the vasculature of insulin resistant humans.
Date Created
2023
Agent

An Examination of School Lunch Consumption and its Relationship with Immediate, Subsequent, Physical Activity

Description

In light of recent school-policy movements that encourage recess be moved before lunch, the present study seeks to examine the relationship between food consumption and immediate, subsequent physical activity (PA) and, more specifically, if a risk would be posed to

In light of recent school-policy movements that encourage recess be moved before lunch, the present study seeks to examine the relationship between food consumption and immediate, subsequent physical activity (PA) and, more specifically, if a risk would be posed to the amount of children's PA if food is not consumed directly before activity. A cross-section study was performed measuring (a) lunch composition (in terms of food groups defined by the USDA's food plate), (b) lunch consumption, and (c) moderate-to-vigorous physical activity (MVPA) during the following recess period, in consenting third through sixth grade students. The relationship between food consumption and percentage of recess time spent in MVPA was determined to be weak. However, the study identified low average provision and consumption rates across all food groups and evaluated this through the lease of current school lunch policy/formatting.

Date Created
2023-05
Agent

PANK2’s Role in Controlling Cellular Coenzyme A Dynamics

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Description
Free coenzyme A (CoASH) carries acyl groups for the tricarboxylic acid (TCA) cycle and fatty acid metabolism, and donates acyl groups for protein posttranslational modifications. Cellular de novo CoASH synthesis starts with a pantothenate kinase (PANK1-3) phosphorylating pantothenate (vitamin B5).

Free coenzyme A (CoASH) carries acyl groups for the tricarboxylic acid (TCA) cycle and fatty acid metabolism, and donates acyl groups for protein posttranslational modifications. Cellular de novo CoASH synthesis starts with a pantothenate kinase (PANK1-3) phosphorylating pantothenate (vitamin B5). Mutations in PANK2 cause a subtype of neurodegeneration with brain iron accumulation (NBIA). The PANKs have differential subcellular distribution and regulatory properties. However, the purpose of each PANK has remained obscure, with knockout mouse models presenting with mild phenotypes unless challenged with a high-fat diet. Based on PANK2’s known activation by palmitoylcarnitine, the PANK2-deficient cells were challenged with palmitic acid (PAL) added to glucose-containing media. The high nutrient mixture generated a surprising “starvation” profile of reduced proliferation, low ATP, AMPK activation, and autophagy upregulation in PANK2-deficient PAL-challenged cells. Further experiments showed that fatty acids accumulated and that PANK2-deficient cells had reduced respiration when provided with palmitoylcarnitine as a substrate, seemingly due to an impaired ability to oxidize fatty acids during PAL-induced Randle Cycle activation. Intriguingly, whole-cell CoASH levels remained stable despite the PAL-induced starvation phenotype, and increasing CoASH via PANK1β overexpression did not rescue the phenotype, demonstrating a unique role for PANK2 in fatty acid metabolism. Even though a direct CoASH deficiency was not detected, there were changes in short chain CoA-derivatives, including acetyl-CoA, succinyl-CoA, and butyryl-CoA, as well as evidence of impaired TCA cycle function. These impairments in both the TCA cycle and fatty acid oxidation implicate a role for PANK2 in regulating mitochondria CoA dynamics.
Date Created
2022
Agent

Examining The Myosin Heavy Chain Distribution in Skeletal Muscle of High-Fat Diet Mice and the Effects of Exercise & Genistein

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Description

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

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.

Date Created
2022-05
Agent

Epigenetic Regulation of Inflammatory Responses in Macrophages

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Description
Innate immunity is regulated at both the transcriptional and epigenetic level. However, the complex epigenetic regulation of inflammatory responses in innate immunity remains to be fully characterized. The objective was to characterize the function of a NAD+-dependent lysine deacetylase SIRT7

Innate immunity is regulated at both the transcriptional and epigenetic level. However, the complex epigenetic regulation of inflammatory responses in innate immunity remains to be fully characterized. The objective was to characterize the function of a NAD+-dependent lysine deacetylase SIRT7 in regulating polarization and inflammatory responses in bone marrow derived macrophages. In primary bone marrow derived macrophages, LPS induced significant pro-inflammatory responses. LysM-Cre induced SIRT7 knockout (KO) male macrophages exhibited enhanced inflammatory responses compared to WT macrophages. Interestingly, we did not observe a similar trend in female cells. In fact, loss of SIRT7 in female macrophages induced weaker proinflammatory responses when challenged with LPS. As an epigenetic co-factor, SIRT7 is known to interact with multiple inflammation related nuclear hormone receptors, such as glucocorticoid receptor (GR), and vitamin D receptor (VDR). Therefore, we examined whether the glucocorticoid or vitamin D induced anti-inflammatory responses are affected in SIRT7 KO macrophages. Preliminary results suggest that both glucocorticoid and vitamin D are still able to inhibit LPS-induced inflammatory responses in SIRT7 KO cells. Future studies using RNA-seq and epigenetic assays will be needed to determine the sex-specific function of SIRT7 in macrophage activation. 
Date Created
2022-05
Agent

Correlational Study Between Types of Motivation and Physical Activity

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Description

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

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.

Date Created
2021-12
Agent

Correlational Study Between Types of Motivation and Physical Activity

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Description

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

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.

Date Created
2021-12
Agent

Exercise, Genistein, and Their Combined Effect on Gut Microbiota and Mitochondrial Oxidative Capacity After 12-Week of a Western Diet on C57BL/6 Adult Mice

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Description
Obesity is one of the most challenging health conditions of our time, characterized by complex interactions between behavioral, environmental, and genetic factors. These interactions lead to a distinctive obese phenotype. Twenty years ago, the gut microbiota (GM) was postulated as

Obesity is one of the most challenging health conditions of our time, characterized by complex interactions between behavioral, environmental, and genetic factors. These interactions lead to a distinctive obese phenotype. Twenty years ago, the gut microbiota (GM) was postulated as a significant factor contributing to the obese phenotype and associated metabolic disturbances. Exercise had shown to improve and revert the metabolic abnormalities in obese individuals. Also, genistein has a suggested potential anti-obesogenic effect. Studying the dynamic interaction of the GM with relevant organs in metabolic homeostasis is crucial for the design of new long-term therapies to treat obesity. The purpose of this experimental study is to examine exercise (Exe), genistein (Gen), and their combined intervention (Exe + Gen) effects on GM composition and musculoskeletal mitochondrial oxidative function in diet-induced obese mice. Also, this study aims to explore the association between gut microbial diversity and mitochondrial oxidative capacity. 132 adult male (n=63) and female (n= 69) C57BL/6 mice were randomized to one of five interventions for twelve weeks: control (n= 27), high fat diet (HFD; n=26), HFD + Exe (n=28), HFD + Gen (n=27), or HFD + Exe + Gen (n=24). All HFD drinking water was supplemented with 42g sugar/L. Fecal pellets were collected, DNA extracted, and measured the microbial composition by sequencing the V4 of the 16S rRNA gene with Illumina. The mitochondrial oxidative capacity was assessed by measuring the enzymatic kinetic activity of the citrate synthase (CS) of forty-nine mice. This study found that Exe groups had a significantly higher bacterial richness compared to HFD + Gen or HFD group. Exe + Gen showed the synergistic effect to drive the GM towards the control group´s GM composition as we found Ruminococcus significantly more abundant in the HFD + Exe + Gen than the rest of the HFD groups. The study did not find preventive capacity in either of the interventions on the CS activity. Therefore, further research is needed to confirm the synergistic effect of Exe, Exe, and Gen on the gut bacterial richness and the capacity to prevent HFD-induced deleterious effect on GM and mitochondrial oxidative capacity.
Date Created
2021
Agent