Kinesiology and Health Sciences

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This is the collection for the University of Waterloo's Department of Kinesiology and Health Sciences. It was known as the Department of Kinesiology until January 2021.

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Characterizing Sex Differences in Lipid Metabolism during an Acute, 30-Minute Bout of Moderate- Intensity Continuous (MIC) Exercise
(University of Waterloo, 2021-01-05) Tremblay, Cory; Devries-Aboud, Michaela
INTRODUCTION: Increased intramyocellular lipid (IMCL) size and storage in the subsarcolemmal region of the myocyte are associated with insulin resistance (IR) and the development of type 2 diabetes (T2D). Women have a higher IMCL content than men yet are at a lower risk for T2D due, at least in part, to the fact that they store IMCL as smaller, more numerous droplets than men. Differences in IMCL turnover may also contribute to the decreased T2D risk. Women utilize a greater proportion of lipids as a fuel source during exercise when compared with men, as evidenced by a lower respiratory exchange ratio (RER). However, whether women rely to a greater extent on IMCL during exercise is equivocal with studies showing greater, similar, or lesser IMCL utilization by women during exercise. IMCL utilization during exercise has been shown to be related to basal IMCL content, which would suggest that women would rely to a greater extent on IMCL during the exercise bout given their increased IMCL storage. Some of the conflicting findings may be due to the fact that the sex-comparative studies conducted to date have focused solely on total IMCL utilization and have not examined whether sex influences region-specific IMCL storage or utilization during endurance exercise. PURPOSE: The aim of this study was to characterize the sex-based differences in substrate utilization, lipid species profile, and enzymes and proteins related to IMCL, lipid and oxidative metabolism following an acute bout of moderate-intensity continuous (MIC) exercise. METHODS: Young, healthy, recreationally active men (n = 12) and women (n = 13) underwent an acute bout of MIC exercise on a stationary cycle ergometer. The MIC exercise session consisted of one, 30-minute cycling bout at 65% VO2 peak with 5-minute breath collections taken at rest, 12, and 25 minutes of exercise. Muscle biopsies were taken from the vastus lateralis muscle prior to and immediately following the exercise bout. All participants were matched for VO2 peak relative to fat-free mass (FFM) to ensure that they were equally trained. As estrogen is known to influence fuel utilization during exercise, women were tested in the midfollicular phase of their menstrual cycle (days 4-9). Enzyme activity assays were used to investigate the activity of β-oxidation and tricarboxylic acid cycle (TCA) enzymes, which included β-HAD and CS, respectively. An untargeted macrolipidomics approach was used to determine sex differences in estimates of fatty acid (FA) content of specific lipid species prior to and following endurance exercise using liquid-chromatography tandem mass spectrometry (LC-MS/MS). Western blot analysis was used to determine the content of proteins involved in lipolysis (ATGL, PLIN3), lipid oxidation (β-HAD, CPT1), and oxidative metabolism (CS, COX II-V). RESULTS: Sex had no effect on RER (p = 0.19), HR (p = 0.44), blood lactate (p = 0.30), or RPE (p = 0.48) throughout exercise. Men oxidized a significantly greater proportion of carbohydrates during the exercise bout (p < 0.001), however whole-body lipid utilization was similar between the sexes (p = 0.92). Protein content for ATGL (p = 0.51), β-HAD (p = 0.80), COX II (p = 0.08), COX III (p = 0.13), COX IV (p = 0.17), COX V (p = 0.94), CPT1 (p = 0.25), CS (p = 0.70), and PLIN3 (p = 0.25) were all similar between men and women. No significant differences in β-HAD (p = 0.54) or CS (p = 0.56) enzyme activity were found; however, relative to baseline, CS activity increased to a greater extent in women (p = 0.04) during exercise. Sex had no effect on detected PC (p ≥ 0.32) or PE (p ≥ 0.23) species. Total abundance of detected TAG content was higher in women than men (p = 0.018), and women had a greater proportion of unsaturated TAGs than men (p = 0.017). Exercise did not influence the lipid profile of PC, PE or TAG species. CONCLUSION: During a 30-minute bout of MIC exercise, whole-body lipid oxidation did not differ between men and women. Furthermore, there was no sex difference in the content of enzymes involved in lipid and oxidative metabolism at rest; however, during the acute bout of MIC exercise CS activity increased to a greater extent in women than men, indicative of a greater increase in oxidative metabolism. Our novel lipidomics analysis provided exciting new insight into the lipid species profiles of PC, PE and TAGs within human skeletal muscle and provides the first report of sex differences in the global lipidome, and serves as the foundation for future studies to complete subsequent lipidomics analyses in human populations.
Characterizing Sex Differences in Skeletal Muscle Anaerobic Metabolism during an Acute Bout of High Intensity Interval Exercise
(University of Waterloo, 2020-09-03) Woodgate, Claire; Devries-Aboud, Michaela
INTRODUCTION: Exercise is known to improve insulin sensitivity (IS); however, its effectiveness may be absent or blunted in women, particularly following high intensity interval (HII) training. Sex differences in anaerobic metabolism during an acute bout of HII exercise have not yet been established and may underpin the lack of effect of HII training on IS in women. Furthermore, it is unclear whether the standardized HII exercise protocol induces similar exercise intensities in men and women which may confound the research findings. PURPOSE: The purpose of the proposed research was to examine whether sex influences the exercise response and/or anaerobic metabolism during an acute bout of high intensity interval exercise. METHODS: Twenty-four young, healthy, recreationally active males (n=12) and females (n=12) were recruited for this study. Men and women were matched according to their maximum aerobic capacity (VO2peak) relative to their fat-free mass (mL O2 • KgFFM-1 • min-1). The exercise protocol consisted of a 5-min warm up, followed by 10 intervals of 60 sec at high intensity (90% HRmax), interspersed with 60 sec at low intensity (50 Watts) and ended with a 5 min cool down. Throughout the exercise bout, heart rate (HR) and rating of perceived exertion (RPE) using the Borg Scale were recorded every minute and blood lactate was recorded every 3 minutes. Muscle biopsies were taken from the vastus lateralis muscle before and after the exercise bout. Muscle samples were analyzed for protein content of metabolic enzymes [phosphorylated pyruvate dehydrogenase (PDH) E1α, and phosphorylated creatine kinase (CK)] and Periodic Acid Schiff (PAS) stained for determination of muscle glycogen utilization. Indirect calorimetry was used to compare indices of exercise intensity and whole-body fuel utilization between men and women during the exercise bout. RESULTS: Sex had no effect on HR (p=0.17) or RPE (p=0.66) throughout the exercise bout; however, %target HR during the high intervals was higher in women (p=0.002). Women exercised at a higher relative %VO2peak during the warm up (p<0.0001), high intervals (p=0.011) and cooldown (p=0.005), but not during the low intervals (p=0.25). Women also worked at a higher wattage during the low intervals when expressed relative to kg lower body fat-free mass (LB FFM) (p<0.0001). During the high intervals, men worked at a higher absolute wattage (p<0.001) and relative wattage when expressed relative to kg LB FFM (p=0.02). Men also expended more energy during exercise (p=0.001) but when expressed relative to kg FFM, there was no difference in energy expenditure between the sexes (p=0.13). Sex had no effect on blood lactate throughout the exercise bout (p=0.35) however lactate AUC was higher in men (p=0.007). Glycogen utilization and phosphorylation status of PDHE1α and CK decreased in both men and women during exercise (p<0.0001, p=0.002 and p=0.002, respectively), with no difference between the sexes. Elevated RER values obtained from indirect calorimetry resulted in invalid whole-body substrate oxidation estimates. CONCLUSION: Markers of HEPT and glycolysis did not differ between men and women, however the greater lactate AUC in men suggests that men relied to a greater extent on anaerobic metabolism during exercise. Importantly, using the standard HII exercise protocol caused women to exercise at a higher %VO2peak, which was mostly likely due to the difference in the relative intensity of the low intervals. Future work should consider using a relative workrate during low intervals to better equate exercise intensity between the sexes.
Does sex influence the effect of mixed mode exercise training on glycemic control, insulin sensitivity and inflammatory markers in overweight/obese, sedentary males and females?
(University of Waterloo, 2023-09-26) Surdi, Julian; Devries-Aboud, Michaela
Introduction: Type 2 diabetes mellitus (T2D) is prevalent within Canada, with a prediction of 5 million people living with this condition by 2025. Exercise reduces the risk of T2D by improving insulin sensitivity. However, recent trials have suggested that exercise training may be less efficacious at improving insulin sensitivity in females compared with males, which could have implications for the prevention and management of T2D in females. The purpose of this research was to examine whether sex influenced the effectiveness of mixed-mode training on glycemic control, insulin sensitivity and inflammation in overweight/obese individuals. Methods: Twenty-seven overweight/obese, sedentary males (n=12) and females (n=15) were recruited for a 12-week mixed-mode, exercise intervention. Prior to training, participants underwent anthropometric, aerobic fitness (V̇O2max test), strength (3-5 RM test) and oral glucose tolerance test (OGTT) assessments. Training consisted of 3 weekly sessions involving 30 minutes of aerobic and 30 minutes of resistance training. Results: There was no sex difference in glucose AUC (p=0.22, ηp2=0.03) or Cmax (p=0.14, ηp2=0.03); however, when adjusted for the glucose dose relative to LBM, males had a higher glucose AUC (p=0.002, ηp2=0.18) and Cmax (p=0.001, ηp2=0.19) than females. TNF-α, (p=0.04, ηp2=0.13) and MIP-1β (p=0.006, ηp2=0.20) were higher in males than females. There was no effect of training on glycemic control, insulin resistance/sensitivity indices, pancreatic β-cell function or inflammatory markers. However, the absolute change in glucose AUC (males: -99.8 mmol/L·120min, females +58.3 mmol/L·120min, p=0.01, d=1.06), Cmax (males: -0.60 mmol/L, females +0.7 mmol/L, p=0.04, d=0.87) and IL-1ra (males: -18.2 pg/mL, females +28.9 pg/mL, p=0.02, d=1.20) differed between the sexes. . Conclusion: Changes in glycemic control and inflammation following training differed between males and females. A sex difference was seen in inflammatory markers; however, further research is required. Finally, females had lower glucose AUC and Cmax relative to LBM compared to males, which questions the use of a standard 75g glucose dose during an OGTT as a measure of impaired glucose tolerance.
Does sex or exercise modality influence post-exercise glucose handling or insulin sensitivity?
(University of Waterloo, 2022-09-20) Beaudry, Kayleigh; Devries-Aboud, Michaela
Exercise has long been recognized for its beneficial effects on glucose handling in both insulin sensitive and insulin resistant populations. However, there is conflicting evidence in regards to the best type and duration of exercise to elicit the greatest benefit on glucose metabolism. Additionally, biological sex is known to influence the metabolic response to both acute and chronic bouts of exercise. Therefore, the purpose of this thesis was to examine the acute effects of three different modes of exercise on post-exercise glucose handling in young, healthy males and females. In Study 1, twenty-four recreationally active males and females (n=12/sex) completed an acute bout of high intensity interval exercise (HIIE, 10x1min at 90% HRmax), to evaluate whether sex influenced the physiological effects of HIIE on post-exercise glycemic control during an oral glucose tolerance test (OGTT). We also examined whether sex differences in post-exercise glycemic control were related to sex differences in muscle metabolism and/or insulin signaling proteins. HIIE increased post-exercise insulin sensitivity in both sexes characterized by the Matsuda and homeostatic model assessment for insulin resistance (HOMA-IR) indices. We also found that HIIE lowered insulin concentration during the OGTT compared to the control OGTT. When normalized for glucose dose relative to lean body mass, glucose area under the curve (AUC) was lower in females than males. While we did not find any difference in total insulin signaling protein content, muscle glycogen utilization or AMPK activation during exercise between the sexes, we found that TBC1D1 Ser237 phosphorylation increased in males, but not females, post-exercise. Overall, these findings indicate that when the glucose dose is normalized for differences in body composition glycemic handling is better in females and that an acute bout of HIIE improves insulin sensitivity equally in healthy males and females. In study 2, we sought to examine the effect of sex on markers of oxidative stress and inflammation following an acute bout of HIIE and during an OGTT. Twenty-four (12/sex) males and females matched for aerobic fitness (V̇O₂peak relative to lean body mass) had muscle biopsies taken at rest and following an acute bout of high-intensity interval exercise (HIIE, 10x1min at 90% HRmax) and blood taken at rest, post exercise, 90 minutes post exercise (immediately prior to an OGTT) and at 60 min during the OGTT. Muscle biopsies were analyzed for markers of oxidative stress/oxidant generation (NOX2, 4HNE, p38 MAPK) and antioxidant status (TRX1, glutathione reductase, GPX1) and blood samples were analyzed for inflammatory markers (IL-6 and TNFα). Following exercise there was an increase in plasma concentrations of IL-6 and TNFα, with IL-6 continuing to increase during the OGTT, with no differences between the sexes at rest or following exercise. We did not see any effect of sex on antioxidant or oxidative stress status; however, we did find that females had higher p38 MAPK phosphorylation at rest compared to males. Overall, these findings suggest that antioxidant status, ROS production and inflammation do not differ between males and females at rest, following an acute bout of HIIE or during a post-exercise glucose challenge. In study 3, twenty-four (n=12/sex) participants completed acute bouts of MIC exercise (30mins at 65% V̇O₂peak) and LLHR (3 circuits, 6 exercises/circuit, 25-35 repetitions/exercise/ circuit) to compare the acute effects of each of these exercise bouts on post-exercise glycemic control and insulin sensitivity. Blood glucose concentrations were lower during a post-exercise OGTT following LLHR RE compared to MIC exercise in males and females. Glucose AUC was also lower in both sexes. In males and females phosphorylated ACC Ser79 increased following MIC exercise only, with no changes following LLHR RE. These findings suggest that LLHR RE is a feasible exercise modality to improve post-exercise glycemic control in males and females. In conclusion we found that LLHR RE decreased blood glucose concentrations to a greater extent than MIC exercise. Additionally, we found that acute HIIE was able to improve post-exercise IS in both sexes. While absolutely glucose concentrations did not differ between males and females, we found that once blood glucose concentrations were normalized to body weight and lean body mass, females had lower glucose concentrations compared to males. The collective results from this thesis indicate that there are some slight differences between the sexes in the metabolic response to acute exercise that may influence pathways responsible for glucose uptake. Overall, the work done in this thesis provides necessary proof of concept for future sex comparative research done in the area of exercise and glucose handling in individuals with insulin resistance.
The Influence of Low-Load High-Repetition Resistance Exercise and Sex on the Metabolic Properties of Skeletal Muscle
(University of Waterloo, 2020-02-04) Pancevski, Kristian; Devries-Aboud, Michaela
INTRODUCTION. The findings of exercise trials have shown that women are better able to initiate aerobic metabolism and are less reliant on anaerobic energy stores. The effect that LL-HR resistance exercise and sex has on substrate oxidation and metabolic species remains unknown. PURPOSE. The purpose of this study was to characterize anaerobic fuel utilization patterns during a bout of LL-HR resistance exercise and to assess whether sex influences fuel utilization during LL-HR. METHODS. Twenty young, healthy participants (n=10 men and women) were recruited and matched for VO2peak relative to fat-free mass and habitual resistance training. The LL-HR bout consisted of a circuit of chest press, leg extension, lat pulldown, hamstring curl, shoulder press, and leg press for 25-35 repetitions at 30% of 1RM with 30s rest between each exercise and 2 minutes rest between circuits. Western blot analysis was completed for relevant metabolic enzymes; GP, PFK, LDH (H and M), PDHE1, PDHK4, CK, AMPD2, MCT (1 and 4), and phosphorylated CK and PDHE1. Content of metabolic species was analyzed before and after the exercise bout and included measures of creatine, ATP, lactate, Pi, pyruvate, and glycogen. MHC staining was used to determine the distribution of fibre type between men and women. Blood lactate was measured and area under the curve (AUC) calculated. RESULTS. Women had a greater type I muscle fibre content than men (p=0.007). Baseline content of all enzymes of interest were similar between men and women (p>0.05). Men had higher concentration of muscle glycogen, lactate, ATP, and Pi than women (p=0.001, p=0.019, p=0.01, and p=0.007, respectively). Phosphorylation status of CK and PDHE1, and content of glycogen and ATP all decreased in men and women with exercise (p<0.001). Phosphorylation state of CK decreased more in women than men (p=0.023); whereas creatine concentration increased during exercise to a greater extent in men than women (p=0.026). Blood lactate increased during exercise (p=0.023), with no differences between the sexes (p = 0.235). CONCLUSION. Men rely to a greater extent on the HEPT system to produce ATP during a bout of LL-HR resistance exercise than women. Interestingly, this occurred despite a greater decrease in phosphorylated CK in women. Overall these findings are supportive of the hypothesis that men rely to a greater extent on anaerobic fuel sources during exercise, which may be in part due to their greater content of type II muscle fibres.
Sex Differences in the Physiological Response to the Modern Fire Environment
(University of Waterloo, 2024-08-30) Pulford-Thorpe, Alexis; Devries-Aboud, Michaela
Due to recent changes in building design and materials, modern structural fires tend towards a ‘ventilation-limited’ fire environment, resulting in globally low levels of oxygen (O2) and increased amounts of carbon monoxide (CO) and smoke. It is unknown how the dynamic hypoxic and hypercapnic environment as a result of the fire impacts an occupant’s physiological and cognitive ability to evacuate. Moreover, it is unknown if physiological sex differences in males and females may further impact egress abilities. This work explored the effects of this dynamic hypoxic and hypercapnic environment on the ability to egress by exposing males and females to sub-incapacitating levels of hypoxic and hypercapnic gases measured in large-scale ventilation-limited fires. Thirty participants (n=15 females) completed three testing days. Day 1 was a familiarization day, intended for participants to familiarize themselves with the experimental protocol of the egress scenario in ambient conditions. Day 2 consisted of five trials of the simulated evacuation scenario wherein real-time changes to O2 and CO2 were administered with CO saturations (%COHb) of 4% and 7%. Day 3 consisted of four trials of the simulated egress scenario wherein changes to O2 and CO2 were carried out in tandem and in isolation. The egress scenario consisted of the following 12.5 minute sequence: 1 min seated pre-test baseline, 5 mins seated, 3.5 mins walking, 4 mins walking carrying a 20lb weight and 2.5 mins seated post-test baseline. This scenario was intended to simulate a realistic evacuation of an occupant from a residential structure, however did not include the more dangerous fire elements (increased temperature, smoke and particulate matter). End-tidal gases, ventilation, heart rate and oxygen saturation were measured continuously. Response (decision, answer and reaction) time was assessed by participants answering a prompt every 15s throughout each trial. The prompts consisted of a directional EXIT sign in which participants had to select the arrow corresponding to the direction of the EXIT sign, as well as a modified Stroop Colour Test. Results demonstrate that females elicited a greater percent change within a condition compared to males for heart rate (p=0.04), tidal volume (p=0.03) and fraction of hemoglobin bound to oxygen (p=0.02). Physiological changes in responses for all participants were significantly greater during the hypercapnia egressing trials compared to hypoxia and control trials (Ventilation: 72±20 L/min, 34±8.9 L/min, 33±6.4 L/min, p< 0.05; tidal volume: 2.3±0.6L, 1.5±0.4, 1.4±0.3, p <0.05). Physiological responses during 4% COHb and 7% COHb trials did not differ other than the fraction of hemoglobin bound to oxygen during pre and post baselines (p<0.05). Overall, the presence of CO2 resulted in the greatest physiological response and coincided with a decrement in ability to complete the egress protocol. Smaller females appeared to be more affected by fire conditions during egress than males. These results indicate that the modern ventilation-limited fire environment results in physiological responses that could negatively impact an occupant’s ability to effectively evacuate.
Sex-based differences in IMCL storage and utilization during an acute bout of high intensity interval exercise (HIIE)
(University of Waterloo, 2023-09-21) Lo, Megan Madeleine; Devries-Aboud, Michaela
INTRODUCTION: The contribution of lipids, particularly intramyocellular lipids (IMCL), to energy production during high intensity interval exercise (HIIE) is not well characterized. Sex influences lipid utilization during moderate intensity aerobic exercise and thus there may be differences in lipid utilization during HIIE as well. There is conflicting evidence as to whether there is a sex difference in IMCL utilization during exercise, which may be a result of improper matching, differences in methodology, or differential use in subcellular regions. PURPOSE: Our study aimed to determine whether IMCL are used during a bout of HIIE and whether sex influences the extent of IMCL utilization. We also examined whether sex or exercise influenced IMCL storage characteristics and morphology. METHODS: Young, healthy, recreationally active males (n=12) and females (n=12) were matched for aerobic fitness (mL O2• kgFFM-1) and performed an acute bout of HIIE (5 min warm up/cooldown @50W, 10 x 1-min @90% HRmax). Biopsies were collected from the vastus lateralis prior to and following exercise for electron microscopic determination of IMCL storage and western blot analysis of proteins related to lipid and aerobic metabolism RESULTS: Carbohydrate oxidation (p<0.0001) and the increase in blood lactate (p=0.02) were greater in males than females during HIIE, with no difference in fat oxidation (p=0.98). Sex had no effect on content of any proteins analyzed (all p>0.08) or on IMCL area density (all p>0.31). IMCL area density did not change during exercise (all p>0.37) and there was no difference in utilization between the sexes (all p>0.47).IMCL feret (p<0.001), perimeter (p<0.004)and average length of IMCL-mitochondria apposition (all p<0.03) were greater in males. IMCL number (p<0.03) and perimeter to area ratio (p<0.006) were greater in females. CONCLUSION: Fat and IMCL are not significant contributors to energy production during HIIE. Comparable rates of fat oxidation and a lesser increase in blood lactate in females suggest that females relied on anaerobic glycolysis to a lesser extent. Excitingly, our region-specific characterization of IMCL morphology establishes a basis for sex-difference investigation into IMCL storage characteristics.
The influence of sex and the human serum environment on fuel storage, skeletal muscle metabolism, and insulin sensitivity
(University of Waterloo, 2025-01-23) Wilkinson, Jennifer; Devries-Aboud, Michaela
Type 2 diabetes (T2D) is a growing global health concern with notable sex-based differences in its pathology. Despite having lower muscle mass and greater fat mass, pre-menopausal females are more insulin sensitive and have a lower prevalence of T2D than males. These discrepancies may be the result of incomplete understanding of the molecular mechanisms underlying glycemic control, insulin resistance and the relationship between sex and insulin sensitivity. As skeletal muscle is the predominate tissue responsible for peripheral insulin sensitivity, the overall purpose of this thesis was to delineate the contribution of sex on factors that affect skeletal muscle insulin sensitivity. The primary aims of this thesis were to determine if 1) sex differences existed in mitochondrial or lipid storage characteristics in aerobically matched participants, 2) sex hormones correlate with metabolic changes in skeletal muscle, and 3) the human serum environment influences proteins associated with metabolism and insulin signaling in mouse skeletal muscle cells (C2C12). In study 1 and 2, muscle biopsies were taken for the determination of mitochondrial and intramyocellular (IMCL) content using electron microscopy and content and activity of proteins related to mitochondrial function and lipid metabolism using western blot and activity assays. Both mitochondrial and IMCL storage characteristics were similar between females and males. However, females have a greater number of mitochondria interacting with IMCL in the subsarcolemmal region (SS) of muscle (p=0.05). For studies 3, 4, and 5, blood was collected from females in the follicular phase and luteal phase of the menstrual cycle and males. Samples were analyzed for estradiol, progesterone, testosterone, insulin, and glucose using commercially available assays. Differentiated C2C12 cells were incubated in 2% human serum for 24 hours and mRNA expression (RT-qPCR), glucose uptake (2-NBDG assay), and protein expression and activation (WB) were measured. We determined that human serum altered mRNA expression, such that estrogen receptor alpha (ERα) expression correlated with estradiol in male serum (Pearson’s r=0.64, p=0.05), but not in female follicular or female luteal serum in C2C12 cells relative to cells incubated with horse serum. Myosin heavy chain I (MHCI) gene expression correlated with estradiol in female follicular (Pearson’s r=0.71, p=0.05) and male serums (Pearson’s r=0.67, p=0.02), but not in female luteal serum in C2C12 cells. Interestingly, the ratio between testosterone and estradiol was positively correlated with ERα gene expression in female follicular serum (Pearson’s r=0.82, p=0.03), but not in female luteal or male serums in C2C12 cells. Further, in C2C12 cells, the activation of protein kinase B (AKT) sans insulin was greater following treatment with female luteal serum than males (p=0.02), but not than female follicular serum, with no difference between female follicular compared to male serums despite similarities in fasting insulin concentrations. Similarly, in C2C12 cells, the activation of phosphatase and tensin homolog (PTEN) without insulin stimulation was lower with female luteal serum when compared to female follicular serum (p=0.05), but not when compared with male serum, with no difference between female follicular and male serum. Finally, glucose uptake with insulin stimulation was increased in female follicular serum (p=0.006), but not in C2C12 cells treated with female luteal or male serums. These findings suggest that insulin sensitivity of skeletal muscle is likely, at least in part, controlled by the hormonal environment in which it is surrounded. Overall, the findings of this thesis found that: 1) aerobically matched females and males have similar mitochondrial characteristics, 2) aerobically matched females and males have similar lipid storage characteristics, 3) sex hormone environment correlates with changes in mRNA, 4) human serum did influence the activation status of proteins associated with insulin-stimulated glucose uptake, and 5) human serum alters insulin-dependent glucose uptake in a similar pattern as seen in whole body trials. These findings provide new insights into the distinct roles of skeletal muscle morphology and serum composition in regulating insulin sensitivity, helping to clarify the interplay between sex, metabolism, and insulin resistance.
Two-weeks of single-leg immobilization alters IMCL storage, mitochondrial content, and insulin signalling in healthy, young women
(University of Waterloo, 2019-05-23) Black, Merryl; Devries-Aboud, Michaela
During limb immobilization and bed rest, there is a significant loss of muscle mass and strength, and an onset of insulin resistance (IR). Subcellular localization of intramyocellular lipids (IMCL) is suggested to regulate the metabolic role of IMCL within skeletal muscle. IMCL stored in the subsarcolemmal (SS) region of the muscle fibre is associated with IR. Total IMCL content is unchanged by immobilization, but endurance training has been found to redistribute IMCL from the SS to the intermyofibrillar (IMF) region. Disuse also decreases mitochondrial content and function and can contribute to IR. The aim of the research presented in this thesis was to determine the effects of disuse on IMCL storage location and apposition with mitochondria and whether these changes are related to disuse-induced defects in insulin signalling. We also determined whether omega-3 fatty acid (FA) supplementation alters the effect of disuse on these outcomes. Young, healthy (n=20) women received omega-3 FA supplement (2.97g of EPA and 2.03g of DHA) or a placebo (isoenergetic and volume equivalent of sunflower oil) for 4-weeks prior to and continuing through 2-weeks of leg immobilization and 2-weeks of recovery. Skeletal muscle biopsies were taken prior to supplementation, pre- and post-immobilization, and after recovery. Electron microscopy was used to determine IMCL size, number, area density, and subcellular localization, as well as mitochondrial area density and subcellular localization. Western blotting was used to examine proteins related to insulin signalling, IMCL metabolism, mitochondrial dynamics, and apoptosis-related signalling. There was no effect of omega-3 FA on any measured parameter. IMCL area density decreased in the SS region during immobilization and recovery due to reduced IMCL size. Central IMF IMCL area density increased with immobilization and returned to baseline during recovery. There was a corresponding decrease in mitochondrial content in the SS region during immobilization and in both the SS region and central IMF during recovery. There was no effect of immobilization or recovery on IMCL or mitochondrial characteristics in the peripheral IMF region. PLIN5 and phosphorylated and total AKT content increased during immobilization and remained elevated in recovery. Accumulation of IMCL in the central IMF region is associated with decreased insulin sensitivity (IS). Previous work has found no relationship between SS IMCL content and IR in women, which is supported by the findings of the current study where SS IMCL area density decreased with immobilization. Surprisingly, there was no loss of insulin signalling protein content during immobilization. The differential effects induced by immobilization on insulin signalling in women may be mediated by estrogen and requires further examination.

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