Kinesiology & Health Science

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Open Access
AMP- Activated Protein Kinase (AMPK) Activation for the Treatment of Mitochondrial Disease
(2014-07-09) Green, Alexander Edward; Hood, David A.
There are multiple copies of mtDNA per cell and each mtDNA molecule contains the information to encode 13 electron transport chain (ETC) proteins. When mtDNA is depleted, there is a decrease in ETC activity. 5' AMP-activated protein kinase (AMPK) is a kinase that can initiate mitochondrial biogenesis and mitophagy. We hypothesized that treating cells harbouring low numbers of mtDNA with an AMPK activator (5-Aminoimidazole-4-carboxamide ribonucleoside; AICAR) would ameliorate the decrease in ETC activity and improve mtDNA copy number. We developed myoblasts (C2C12 cells) depleted of mtDNA with long-term ethidium bromide treatment. We treated selected clones for 24 hours with 1 mM AICAR to activate AMPK. AICAR treatment decreased markers of mitochondrial biogenesis, mitochondrial function (e.g. maximal cellular respiration), and mitochondrial degradation. Thus, failing to increase the energy producing capacity of the cell, activation of AMPK may have induced an energy sparing mechanism.
Open Access
Associations Between Urinary Concentrations of Non-Persistent Pesticide Exposure, Polycyclic Aromatic Hydrocarbons and Cardiometabolic Health
(2015-01-26) Ranjbar, Mahsa; Kuk, Jennifer
Recent literature has established environmental pollutants to be associated with health risk. However, it remains unclear whether the less studied organophosphate (OP) pesticides and polycyclic aromatic hydrocarbons (PAH) influence cardiometabolic health independent of BMI. The first study in this thesis used 2,227 participants from the National Health and Nutrition Examination Survey (NHANES). It was demonstrated that most OPs are associated with a detrimental cardiometabolic health outcome with higher BMIs amplifying health risk. However one metabolite (dimethylphosphate) was associated with advantageous health outcomes. In the second study, 6,159 NHANES participants were used to demonstrate that high levels of PAH are positively and negatively associated with obesity. PAH was also associated with a greater risk of metabolic syndrome, dyslipidemia, hypertension, and type 2 diabetes, independent of BMI. Thus, OP and PAH influence obesity-related health risk, however, more research is needed to further elucidate the mechanistic pathways associated with OP, PAH and health.
Open Access
Effect of Denervation on the Regulation of Mitochondrial Transcription Factor a Expression in Skeletal Muscle
(2015-01-26) Tryon, Liam Dennis; Hood, David A.
The most rapid decline in myofiber size and mitochondrial content during denervation, a muscle disuse model, occurs during the first week following the onset of the stimulus. In this study, we analyzed the expression of Tfam, a critical mitochondrial transcription factor involved in the orchestration of mitochondrial biogenesis, at multiple levels during denervation. Tfam transcriptional activation was depressed during the early stages of denervation but was counteracted by increases in the stability of the Tfam mRNA, an effect which could not be accounted for by the protein expression of select RNA-binding proteins. Denervation reduced Tfam mitochondrial import, which was associated with reductions in mitochondrial DNA transcription. These data highlight that there are multiple factors affecting the expression and activity of the Tfam transcript and protein during denervation. This work also emphasizes the importance of mitochondrial protein import in the regulation of Tfam function, and subsequently mitochondrial content, during muscle disuse.
Open Access
Sex- and Experience-Related Differences in Bimanual Coordination Development
(2015-01-26) Albines, David; Sergio, Lauren
Sex- and experience-related differences in bimanual coordination have been found previously but are often reported separately. Here, we characterize visuomotor skill performance in relation to age, sex, and athletic experience in order to indirectly gain insight into the neural processes that underlie this advanced level of eye-hand coordination. We use a novel precision bimanual task composed of a modified washer-peg board. We recruited three age and two experience groups (9-10, 11-12 and 13-15, elite versus house league). We also developed a Whole-hand bimanual task in order to account for any manual dexterity discrepancies. The results show that the effect of skill and sex are not seen until later years developmentally, at that point there is a strong effect of sex on bimanual coordination. Future research that aims to look at the development of motor skills and control should also look at sex and experience effects.
Open Access
The Role of the Dorsal Premotor and Superior Parietal Cortices in Decoupled Visuomotor Transformations
(2015-01-26) Sayegh, Patricia; Sergio, Lauren
In order to successfully interact with objects located within our environment, the brain must be capable of combining visual information with the appropriate felt limb position (i.e. proprioception) in order compute an appropriate coordinated muscle plan for accurate motor control. Eye-hand coordination is essential to our independence as a species and relies heavily on the reciprocally-connected regions of the parieto-frontal reach network. The dorsal premotor cortex (PMd) and the superior parietal lobule (SPL) remain prime candidates within this network for controlling the transformations required during visually-guided reaching movements. Our brains are primed to reach directly towards a viewed object, a situation that has been termed a “standard” or coupled reach. Such direct eye-hand coordination is common across species and is crucial for basic survival. Humans, however, have developed the capacity for tool-use and thus have learned to interact indirectly with an object. In such “non-standard” or decoupled situations, the directions of gaze and arm movement have been spatially decoupled and rely on both the implementation of a cognitive rule and on online feedback of the decoupled limb. The studies included within this dissertation were designed to further characterize the role of PMd and SPL during situations in which when a reach requires a spatial transformation between the actions of the eyes and the hand. More specifically, we were interested in examining whether regions within PMd (PMdr, PMdc) and SPL (PEc, MIP) responded differently during coupled versus decoupled visuomotor transformations. To address the relative contribution of these various cortical regions during decoupled reaching movements, we trained two female rhesus macaques on both coupled and decoupled visually-guided reaching tasks. We recorded the neural activity (single units and local field potentials) within each region while the animals performed each condition. We found that two separate networks emerged each contributing in a distinct ways to the performance of coupled versus decoupled eye-hand reaches. While PMdr and PEc showed enhanced activity during decoupled reach conditions, PMdc and MIP were more enhanced during coupled reaches. Taken together, these data presented here provide further evidence for the existence of alternate task-dependent neural pathways for visuomotor integration.
Open Access
Tricyclic and SSRI Usage Influences the Association Between BMI and Health Risk Factors
(2015-01-26) Carlton, Kristin Jennifer; Kuk, Jennifer
The prevalence of antidepressant use is increasing. Past studies have reported that the use of antidepressants can influence cardiovascular risk factors including obesity, blood lipids and blood pressure (BP). However, because antidepressants have the potential to influence both body weight and cardiovascular disease (CVD) risk, it is currently unclear if antidepressant use alters CVD risk independent of obesity. Therefore, the aim of this manuscript was to examine if the type of antidepressant (Selective-Serotonin Reuptake Inhibitors (SSRIs) or Tricyclic antidepressants (TCAs)) used influenced the association between obesity and CVD risk. This study demonstrated that for a given body mass index (BMI) certain antidepressant use was associated with exacerbated health risk factors and CVD risk. Clinically, this may indicate that the differences in body weight observed with the use of SSRIs and TCAs may not be associated with the normally expected differences in cardiovascular risk.
Open Access
Subverting the Ideal? Canadian Female Bodybuilders' Resistance of Idealized Femininity
(2015-01-26) Tajrobehkar, Bahar; Safai, Parissa
Women’s bodybuilding challenges the social construction of the female body as frail or limited (Bunsell, 2013). In the context of competitive bodybuilding, however, women’s colonization of the muscular body is policed through judging criteria that require expression of femininity on stage through gestures, posing, make-up and hairstyle (Lowe, 1998). This study examined the experiences of nine female competitors to understand the ways in which they perceive and negotiate the expectations of idealized femininity within current bodybuilding competitions. Qualitative methods (in-depth, semi-structured interviews and ethnographic fieldwork) were used. The analysis was informed by feminist deconstructions of sex, gender and sexuality in sport (Dworkin & Wachs, 2009) as well as by Foucauldian understandings of discipline/surveillance and technologies of the self (cf., Rabinow & Rose, 2003). The data gathered went beyond this focus to underline the contradictory views that some female bodybuilders hold of female muscularity and femininity. These views pointed to the influence of broader cultural perceptions on alternative versions of femininity constructed by bodybuilders. This influence, in turn, seemed to play a role in the bodybuilders’ acceptance or tolerance of the competition judging criteria. In short, the analysis demonstrated that the participants were able to negotiate the judging criteria, albeit at times reluctantly and with frequent expressions of criticism and disapproval.
Open Access
Women's Preferences for Cardiac Rehabilitation: Do Home-Based and Women Only Programs Better Meet Their Needs?
(2015-01-26) Andraos, Christine; Grace, Sherry
Background: Although cardiac rehabilitation (CR) is effective, women report programs do not meet their needs. The objectives of the study were to describe women’s: (1) adherence to CR allocation, (2) satisfaction by model attended, and (3) CR preferences. Design & Methods: Female patients were randomized to mixed-sex, women-only, or home-based CR. Patients were recruited from six hospitals. Consenting participants were asked to complete a survey. Eligible patients were randomized. Participants were mailed a follow-up survey. Results: Overall 169 (18.6%) patients were randomized, of which 116 (68.6%) were retained. Forty-five (26.6%) participants did not receive the allocated model. Satisfaction was high (mean=4.23±1.16/5; p=0.85), but women-only participants felt more comfortable in their workout attire (p=0.003), and perceived the environment as less competitive (p=0.02). Patients preferred mixed-sex (n=44, 41.9%) and women-only (n=44, 41.9%) CR, over home-based (n=17, 16.2%). Conclusion: Females were highly satisfied regardless of CR model attended, but preferred supervised programs most.
Open Access
Mental Health and Mental Healthcare Utilization in Canada's Immigrant and Ethnocultural Populations
(2015-01-26) Islam, Farah Tazveena; Tamim, Hala
One in five Canadians will experience a mental illness or addiction during their lifetime, but only 50% of those with a current diagnosis of mental illness will actually seek care (Lesage et al., 2006). Canada is home to growing immigrant and ethnocultural populations. Factors of migration, ethnicity, and racialization are important social determinants of mental health. However, Canada’s Mental Health Strategy identifies the lack of information available on these diverse populations and calls for further research in order to develop mental health programming (Mental Health Commission, 2012). This three-part doctoral dissertation sought to address these research gaps at the national-level, provincial-level, and community-level. The first study, “South Asian Populations in Canada: Migration and Mental Health,” was a national-level epidemiological analysis, which examined the prevalence and characteristics of mental health outcomes for South Asian immigrant populations in Canada compared to their South Asian Canadian-born counterparts. The second study, “The Epidemiology of Mental Healthcare Utilization by Service Provider Type for Ontario’s Immigrant Populations,” was a provincial-level epidemiological analysis examining the prevalence and characteristics of past-year mental health consultation by service provider type for Ontario’s immigrant populations. Lastly the third study, “The Barriers and Promoters of Seeking Mental Healthcare: A Mixed Methods Study of Bangladeshi Populations in Toronto,” was a community-level mixed methods project investigating the barriers and promoters of seeking mental healthcare identified by Toronto Bangladeshi newcomer and longer-term immigrant populations. These three studies seek to address the knowledge and research gaps identified by Canada’s Mental Health Strategy (Mental Health Commission, 2012). This research provides important information on the mental health outcomes, mental health service utilization, and barriers and promoters of mental healthcare access for immigrant and ethnocultural populations in order to inform the development of a mental health system inclusive of Canada’s diverse populations.
Open Access
Gait, Balance Recovery and Balance Confidence after Total Knee Replacement: Differences between Younger and Older Patients
(2015-01-26) Street, Brian David; Gage, William
Total knee replacement (TKR) is the gold standard treatment for improving mobility and relieving pain associated with end-stage knee osteoarthritis (OA) when other modalities have failed. Patients demonstrate significant improvements compared to pre-TKR levels, however deficiencies in function and mobility remain when compared to healthy controls. Recent national joint replacement registries have reported a substantial increase in the number of TKR procedures performed on younger patients. Over the last decade in Canada, the largest relative percent increase (≈300%) in TKRs has occurred to patients who were between 45-54 years of age. Although this younger patient group (<55 years old) is rapidly growing, the vast majority of the literature investigating TKR outcomes has been based upon the ‘typical’, older TKR patient (≥ 65 years old). This has created a therapeutic dilemma for clinicians, having little empirical data to formulate explicit statements or recommendations regarding how TKR will affect this younger population, and a concern with prosthesis failure and revision surgery, there is a hesitation to perform TKR on the younger knee OA patient. Age-related deterioration in sensory information acquisition and musculoskeletal function has been observed between younger and older adults in the absence of knee OA and TKR, and has been linked to an increase in fall risk and falls. These age-related deficits observed in healthy adults may also distinguish younger and older TKR patients, which would have important implications to the surgical and rehabilitation practice. Currently, there are a limited number of published reports examining age-related differences in TKR patients and this gap in the literature warrants investigation. Therefore, the goal of this thesis is primarily to investigate the younger TKR patient and to compare their observations to that of the older, ‘typical’ patient and to their healthy age-matched controls.
Open Access
Yoga, Women, and Cancer: Experiences in a Specialized Yoga Program
(2015-01-26) Cowling, Angela Elizabeth; Safai, Parissa
The purpose of this project was to better understand the experiences of women with cancer who participated in a specialized yoga program at a studio in Toronto. The focus on this particular location served as a case study of such specific physical activity programming for special populations. This study examined who participated in this program and explored their reasons for participating in efforts to better understand their thoughts on health, including the imperative to be healthy (i.e., healthism), illness, physical activity (specifically yoga), and the interrelationships between such issues in their lives. Using qualitative research methods, semi-structured interviews were completed in order to gain a better understanding of the lived experiences of women who have participated in yoga classes while having or recovering from an illness. Participants consisted of five women in remission from cancer who practiced yoga prior to their diagnoses, during treatment, and throughout recovery. Findings indicated participants' motivations for practice centered on achieving holistic health and experiences during the cancer journey were greatly influenced by their socioeconomic privilege. In addition, results showed an overwhelming focus on positivity and the adoption of healthism. Future implications of this research may be to modify existing specialized yoga programs and provide recommendations on the use of yoga in cancer care, as well as consider how to approach the influential "tyranny of cheerfulness" in cancer culture and combat dominant healthist ideals. In addition, this project will contribute to the existing body of sociocultural research in health and physical activity and increase knowledge of experiences in this population.
Open Access
Waist Deep in Mud: A Socio-Cultural Analysis of Tough Mudder
(2015-01-26) Vlahos, John; Safai, Parissa
The Tough Mudder (TM) event is a non-stop, multidiscipline, individual and team endurance obstacle race. This paper examines how TM participants identify withand understand TM and how in turn, it contributes to their self-understanding as risk-takers in sport. It also identifies whether these participants are part of a social group whose preference for such a sport practice is linked to their social location. Qualitative methods (in-depth, one-on-one semi-structured interviews as well as participant observation) were used. The analysis of the data exposed disparity amongst perceptions of both study participants’ understanding of TM as being all inclusive as well as their self-categorization as recreational athletes. Additionally, a lack of vocalization of the type of risk involved in such events and the reification of reproduced values of pain and injury tolerance emerged as dominant themes.
Open Access
Association Between Obesity and Cardiometabolic Health in Asian-Canadian Sub-Groups
(2015-01-26) Nie, Xin Jason; Ardern, Chris
Purpose: To examine the association between the WHO’s Asian specific trigger points representing ‘increased risk’ (BMI ≥23 kg/m2) and ‘high risk’ (BMI ≥27.5 kg/m2) with cardiovascular-related conditions in Asian-Canadian sub-groups. Methods: Six cycles of the Canadian Community Health Survey (2001-2009; N=18 794) were pooled and weighted; multivariable logistic regression was used to estimate the odds of cardiovascular outcomes. Results: Versus South Asians, Filipinos had higher odds of ‘≥1 cardiometabolic condition’ (OR=1.29). Compared to the normal weight category in each ethnic group, the association between excess adiposity on ‘≥1 cardiometabolic condition’ was highest among Chinese (‘increased risk’: OR=3.6; ‘high risk’: OR=8.9). Compared to ‘normal weight’ South Asians, those in the ‘high risk’ groups (except Southeast Asian, Arab, and Japanese) were approximately 3-times as likely to report ‘≥1 cardiometabolic condition’. Conclusions: The relationship between overweight, obesity, and health risk varied within Asian sub-groups, and was strongest for South Asian and Filipino.
Open Access
Exploring the Continuity of Sports Participation: The Role of Community Sport Clubs In the Sport Development Process
(2015-01-26) Wolman, Lauren Yve; Fraser-Thomas, Jessica L.
Athletes are often faced with various life and athletic transitions, which can lead to a decline or even a drop-out in sport participation (Freysinger & Ray, 1994; Lim, Warner, Dixon, Berg, Kim, & Newhouse-Bailey, 2011; Lunn, 2010; Tammelin, Näyhä, Hills & Järvelin, 2003, Wyllemann & Lavallee, 2004). In Canada, the most significant decline in sport participation occurs between the ages of 15 to 24 years (Statistics Canada, 2012), when many graduate from secondary and/or post-secondary education. The purpose of this research was to explore the role of community sport clubs in facilitating sport participation in the sport of rugby union in a large Canadian city, with a specific focus on the transition from youth to adult sport. Two qualitative studies were conducted which examined a) athletes’ perspectives of the psychosocial factors that influenced initial involvement and continued participation on a community sport club and b) administrators’ perspectives of the role of community clubs in facilitating sport development and the continuity of sport participation into adulthood. Findings demonstrated that early exposure and access to sport can increase athletes’ awareness and initial involvement with community clubs and strong school-club partnerships can facilitate athletes’ continued involvement in structured competitive sport. To build sport commitment and club loyalty, strategies should be implemented to ensure seamless transitions between junior and senior sport and programs should provide a balance between the competitive and social elements of sport. Lastly, providing flexible programming and opportunities for athletes to transition into leadership roles can extend athletes’ lifelong involvement in sport. Findings are discussed in the context of practical implications (e.g., community sport clubs’ strategic planning) and future research directions (e.g., examining different sporting environments)
Open Access
Physical Literacy: From Theory to Practice Exploring Experiences of New Health and Physical Education Teachers
(2015-01-26) Tristani, Lauren Katherine; Fraser-Thomas, Jessica L.
With growing rates of child and youth obesity and overweight, school health and physical education (H&PE) has been proposed as a vehicle through which to enhance children’s healthy physical and psychosocial development (e.g., Ebbeling, Pawlak & Ludwig, 2002). Physical literacy is a concept recently introduced into Ontario’s H&PE curriculum, with the belief that it will raise the quality of H&PE (Ontario Ministry of Education, 2010), by providing students with the skills and confidence to be active for life (McKean, 2013). The purpose of this study was to examine new health and physical education teachers’ education experiences in relation to physical literacy, with a specific focus on their education and training, perceptions, and implementation of physical literacy into school H&PE settings. Participants (N =10) included 6 males and 4 females new H&PE teachers, emerging from Faculties of Education within the province of Ontario. Using grounded theory methodology (Strauss & Corbin, 1998), data analysis followed several coding procedures geared toward theory development. Results suggest that various breakdowns were occurring within the three major educational components (i.e., formal teacher education, curriculum, and teaching practicum), hindering the successful integration of physical literacy in practice. Findings are considered in relation to existing teacher education and H&PE research and a grounded theory of the educational components associated with the successful integration and implementation of physical literacy is presented. Practical implications and future research directions arising from this exploratory theory are discussed.
Open Access
Cost-Effectiveness of Exercise Facilitation Post-Cardiac Rehabilitation
(2015-08-28) Kana, Kujaany; Grace, Sherry L.
Background: Physical activity declines post-cardiac rehabilitation (CR) suggests the need for an exercise maintenance intervention. The study objectives were to assess (1) health-care resource utilization, (2) QALYs, and (3) intervention cost-effectiveness. Methods: A randomized controlled trial of post-CR participants allocated to: (a) exercise facilitator intervention, or (b) usual care. Participants were randomized and asked to complete a baseline and follow-up surveys. Results: Overall, 297 (16.7%) graduates consented (50.2% intervention), of which 276 (92.9%) were retained at the 26 week and 264 (88.9%) were retained at 52 weeks. At 26 weeks, there were significant differences in emergency department mean visits (0.33±0.71 [control], 0.22±0.51 [intervention]) and hospitalizations (0.16±0.39[control], 0.07±0.28[intervention]). At 52 weeks, interventional participants had higher hospitalizations (p<0.05). There were minimal differences in quality of life (QoL) means score and QALYs throughout the trial among groups. Conclusion: These results suggest that there was an early cost-benefit associated with the intervention from a societal perspective, but this was not sustained at 52 weeks.
Open Access
Analyzing Vitamin D3 Supplementation and Deficiency in the Spinal Cord of Transgenic G93A Mouse Model of Amyotrophic Lateral Sclerosis
(2015-08-28) Moghimi, Elnaz; Hamadeh, Mazen J.
Vitamin D3 (D3) may impact ALS, a motoneurodegenerative disease. The study analyzed D3 supplementation at 50x the adequate intake (AI) and restriction at 2.5% the AI in the spinal cord of transgenic G93A, a mouse model of ALS. At 25 d, mice were provided food ad libitum with adequate (AI;1 IU D3/g feed), high (HiD; 50 IU D3/g feed) or deficient (DEF; 0.025 IU D3/g feed) D3. At 113 d, the spinal cords underwent protein analysis. HiD females exhibited D3 toxicity, evidenced by increased oxidative damage and apoptosis and lower antioxidant capacity vs. AI. HiD males exhibited lower oxidative damage, inflammation, apoptosis and neuron damage vs. AI. DEF females exhibited higher inflammation and a compensatory increase in GPx1 vs. AI. DEF males exhibited higher lipid peroxidation and lower antioxidant capacity vs. AI. In G93A mice, non-toxic doses of D3 attenuate disease pathophysiology, whereas deficiency worsens it in a sex-specific manner.
Open Access
Quantification and Evaluation of the Biomechanical Behaviour of the Trunk During Fundamental Tasks: Should the Thoracic Spine be Considered?
(2015-08-28) Schinkel-Ivy, Alison Nicole; Drake, Janessa D. M.
Thoracic spine research is sparse relative to the lumbar spine. A better understanding of thoracic spine mechanics may provide insight into pain mechanisms in both spine regions. This dissertation quantified and evaluated the biomechanical behaviour of the thoracic spine during fundamental tasks, to determine if monitoring the thoracic spine is necessary in the investigation of spine mechanics. The number of trials required for repeatable and reliable trunk kinematic and muscle activation measures across maximal ranges-of-motion (ROM) were determined (Study #1). Thirty participants performed 10 trials of upright standing and maximal trunk ROM. Most measures demonstrated high repeatability, with two to five trials required. The head and arm positions enabling maximal spinal ROM were determined in Study #2 using 24 participants, as relationships have been shown in head, arm, and upper back motion. The greatest angles were produced with the active head–loose arm, active head–crossed arm, and active head–abducted arm positions for maximum flexion, bending, and twisting, respectively. Studies #3 and #4 determined the segments and superficial muscles that were necessary to quantify the motion and muscle activation characteristics of the trunk, specifically the thoracic spine. Thirty participants performed upright standing, maximum trunk ROM, and thoracic ROM. A four-cluster marker set quantified motion for most movement tasks. Of the 16 muscles tested, 10–14 were necessary to evaluate trunk muscle activation. These studies provided insight into thoracic function in relation to the lumbar spine. Lumbar co-contraction was quantified during thoracic movements in Study #5. Thirty participants performed upright standing, maximum trunk ROM, and thoracic ROM. Thoracic flexion, bending, and twisting elicited 67%, 45%, and 55% greater co-contraction in the lumbar region than upright standing, demonstrating that the thoracic spine impacts the muscular response of the lumbar spine. These studies quantified and characterized the biomechanical behaviour of the thoracic spine during fundamental tasks. As the thoracic spine demonstrated differences in motion and muscle activation characteristics along its length and compared to the lumbar spine, knowledge of thoracic spine behaviour and interactions may aid in clarifying the behaviour of and elucidating pain mechanisms within the thoracic and lumbar spine regions.
Open Access
The Interplay Between PGC-1 and Autophagy During Metabolic Alterations in Skeletal Muscle
(2015-08-28) Vainshtein, Anna; Hood, David A.
PGC-1α is a transcriptional co-activator well established as a potent regulator of oxidative metabolism in skeletal muscle. This co-activator mediates metabolic adaptation to exercise by orchestrating mitochondrial biogenesis. PGC-1α is also integral for the maintenance of muscle mass and function during atrophic conditions. Autophagy is a highly conserved proteolytic pathway responsible for the degradation of dysfunctional organelles and protein aggregates through the lysosomal machinery. Autophagy is upregulated during metabolic distress and is essential for cell survival. While PGC-1α has been extensively studied in the context of skeletal muscle adaptations, its role in autophagy has not been dissected. To this end, the purpose of this dissertation was to examine the interplay between PGC-1α and autophagy in skeletal muscle in the spectrum of muscle contractile states. We first assessed the role of PGC-1α in the regulation of autophagy and mitophagy during chronic muscle disuse in the form of denervation. To do this we denervated wildtype (WT), PGC-1α knockout (KO) as well as PGC-1α overexpressing (Tg) animals. We found that autophagy and mitophagy flux were compromised in KO animals both basally, and in response to denervation, resulting in a myopathic phenotype. In the Tg animals we uncovered enhanced levels of certain autophagy and lysosomal markers, but surprisingly noticed reduced targeting of mitochondria for degradation. Overall we concluded that PGC-1α is important for the fine-tuning of autophagy in skeletal muscle based on cellular metabolic state, but that it is not required for this process. Next we evaluated the role of PGC-1α in mitochondrial turnover following an acute bout of exhaustive exercise. We found that in the absence of PGC-1α, exercise-induced mitochondrial turnover was compromised, as evident by reduced expression of mitochondrial genes and diminished autophagy/mitophagy induction, as well as flux. Collectively, our data demonstrate that PGC-1α is instrumental in maintaining mitochondrial health in skeletal muscle through enhancing organelle turnover. Moreover, PGC-1α can fine-tune autophagy/mitophagy in a manner that is specific to cellular metabolic state.
Open Access
Effects of Metformin and Combinatory Derived Factors of Adipose Tissue on Prostate Cancer Growth
(2015-08-28) Nazeer, Beshoy; Connor, Michael K.
Obesity is a growing concern worldwide and is associated with increased risk of prostate cancer (PCa) and poor patient prognosis. Metformin (MET) is reported to be protective against PCa in type 2 diabetics as they are at a reduced risk of developing PCa and have a better prognosis if they do in fact develop PCa. My thesis examined the effects of MET on two prostate cancer cell lines, LNCaP and PC3 cells. MET caused alterations in morphology and cell detachment in both cell lines. MET counteracted the effects of leptin which was independent of AMPK activation. PC3 cells incubation with conditioned media and treated with MET caused increased AMPK activation and decreased AKT activation. MET was found to act independently of AMPK although it caused an increase in AMPK activation in PC3 cells. It appears that MET represents a promising adjuvant therapy for obese PCa patients.