Ischemic heart disease is the largest cause of death due to cardiovascular origins. A better understanding of the mechanisms responsible for ischemic heart disease increases the potential for therapies. This will lead to decreased mortalities in Canada and around the world. Nutritional interventions have gained increasing attention as causes or treatments for cardiovascular disease. For example, trans fats (TFAs) have both beneficial and deleterious effects on cardiovascular disease [1]. In this study, we would like to examine this phenomenon. We contrast the effects of two different TFAs on cardiomyocyte viability. We compare the industrially produced trans-fat elaidic acid (EA) and the ruminant trans-fat vaccenic acid (VA) on apoptotic and autophagic markers during non-ischemic (control), ischemic (ISCH) and ischemia/reperfusion (IR) conditions. Rat cardiomyocytes are exposed to medium containing fatty acids conjugated with bovine serum albumin for 24 hours. VA and EA have no significant effect on biomarkers of apoptosis or cell death. Interestingly, a similar effect is observed with autophagic and apoptotic markers of LDLr-/- mice whose diets were supplemented with VA or EA. Cells pre-treated with EA prior to 60 minutes of simulated ISCH and 120 minutes of IR increased cell death compared to control through augmented apoptosis. VA decreases the number of dead cells during ISCH and IR. However, the apoptotic parameters remain unchanged. We also observe that VA decreases oxidized phospholipid content in non-ischemic conditions. We conclude that not all TFAs are deleterious to the heart. EA is toxic to cardiomyocytes with or without ISCH or IR whereas VA is cardioprotective during IR and ISCH conditions. We believe VA decreases oxidized phospholipid content to produce this cardioprotective effect. For the purposes of comparison, we examined the effects of α-linolenic acid (ALA), an essential polyunsaturated fatty acid found in foods like flaxseed. Omega-3 fatty acids have been associated with improved cardiovascular outcomes. Here, isolated adult rat cardiomyocytes from male Sprague Dawley rats were exposed to medium containing ALA for 24 hours and then exposed control, ISCH or IR conditions. Cell death increases during ISCH and IR. An increase in DNA fragmentation and caspase-3 activity was observed in both the ISCH and IR conditions. Pre-treatment of the cells with ALA subsequently inhibits cell death during ISCH and IR challenge and significantly reduced both DNA fragmentation and caspase-3 cleavage during ISCH and IR. Cardiomyocyte resting Ca2+ increased and Ca2+ transients decreased during ISCH or I/R but ALA pre-treatment did not improve either parameter significantly. We hypothesize that apoptosis is initiated through phosphatidylcholine oxidation within the cardiomyocytes. Pre-treatment of cells with ALA resulted in a significant incorporation of ALA within cardiomyocyte phosphatidylcholine. Two pro-apoptotic oxidized phosphatidylcholine (OxPC) species, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) were significantly increased during both ISCH and IR. ALA pre-treatment significantly decreased the production of POVPC and PGPC during ISCH and I/R. It is concluded that ALA protects the cardiomyocyte from apoptotic cell death during simulated ISCH and IR by inhibiting the production of specific pro-apoptotic OxPC species. In summary, we observe a differential effect of ALA, VA and EA on parameters of cardiomyocyte viability during ISCH or IR.

No description available.

Assessment of body fat percentage is desirable to identify health risks associated with obesity. There are few studies that have compared the assessment of body fat between air displacement plethysmography and dual-energy x-ray absorptiometry, particularly related to age and gender differences. The purpose of this study was to determine if body fat percent estimates differ depending on age and/or gender between air displacement plethysmography (Bod Pod, Life Measurements Instrument, Concord, CA) and dual-energy x-ray absorptiometry (DEXA, General Electric Medical Systems, Lunar Prodigy, Madison, WI). Sixty subjects were studied: 15 men and 15 women, 22-35 years and 15 men and 15 women, 55-80 years. Subjects were excluded if they competed in athletics or high-level exercise training in the last year. Standard calibration and testing procedures were used for both methods. Both methods were administered at least twice to evaluate reliability and were repeated a third time if the first two measures differed by >2%. Differences between methods for age groups and gender were analyzed using ANOVA and reliability comparisons between the body composition methods were evaluated with correlation coefficients and Bland-Altman plots. Using data for all subjects, DEXA (r = .996) and Bod Pod (r = .985) both showed good reliability. However, in younger females the reliability of the Bod Pod (r = .911) was lower. Sixteen of the 60 subjects required a third trial for the Bod Pod, whereas all repeated DEXA measures were consistent. The deviation between trial 1 and 2 for the DEXA (.6%) was significantly less than that in the Bod Pod (1.5%). Significant interactions between the body composition method and age group were found. Mean body fat percentage in the younger group was higher in the DEXA (24.1 + 1.1%) than the Bod Pod (23.0 + 1.3%) however, in the older group it was found to be lower in the DEXA (33.9 ± 1.1%) than the Bod Pod (37.2 ± 1.3%). Both the DEXA and the Bod Pod were reliable but repeated DEXA measures were more consistent than the Bod Pod measures. Bod Pod estimates of body fat percentage were lower for younger subjects, yet higher for older subjects compared to DEXA measurements. / School of Physical Education, Sport, and Exercise Science

Male Sprague-Dawley rats were used to determine whether insulin resistance develops between 1.5-4.0 months of age and whether it is related to aging or the development of obesity. Animals were randomly placed into a single 1.5 months old group (1.5 CN) or raised in one of three 4.0 month old groups; exercise trained (ET), pairfed (PF), or sedentary control (4.0 CN). The ET group was fed ad Iibitum and had free access to a spontaneous exercise wheel, while the PF group was fed to maintain equal body weight with the ET group. The young group was sacrificed with nembutal injection (45 mg/kg body weight) at 1.5 months while the other three groups were sacrificed at 4.0 months of age. Epididymal fat pads were removed, digested with collagenase (5 mg/ml) and the isolated cells sized and assayed for 2-deoxyglucose transport over a range of insulin concentrations (0-1000 µU/ml). Body composition (percent fat, bone and muscle) was performed on the carcasses of these animals at a later date. The 2-deoxyglucose transport of the 1.5 CN group was significantly greater than the 4.0 CN group at insulin concentrations of 50, 250 and 1000 uU/ml and significantly greater than all 4.0 months groups at 1000 11U/ml- The adipocyte size was significantly smaller in the 1.5 CN group followed in ascending order by the ET, PF and 4.0 CN group. The body compositions demonstrated the expected trends as the 1.5 CN group had the highest percent bone and muscle while demonstrating the lowest percent fat. The ET group was most able to maintain the body composition of the 1.5 CN group, while the PF and 4.0 CN groups were least able to maintain this composition respectively.The results indicate that: 1) Adipocyte insulin resistance develops in the rat between 1.5 and 4.0 months of age. 2) This development of insulin resistance is related to obesity and not to aging. 3) Exercise may prevent the development of insulin resistance by preventing adipocyte hypertrophy. 4) Exercise helps maintain optimal body composition. These results should be of interest to type II diabetics as an exercise program may decrease their adipocyte size, enhance body composition and decrease insulin resistance.

No description available.

No description available.

Drosophila Fat is a large atypical cadherin molecule. Genetic assays show that Fat has multiple function, however, the mechanism of Fat function is poorly understood. Hence, I undertook a biochemical approach to determine the mechanistic function of Fat. Previous data indicated that Fat might be processed; I further confirmed the precursor-product relationships between these proteins. I then looked at sub cellular localization of Fat. My preliminary data suggests that the smaller 110 kDa forms of Ft goes to the nucleus. To characterize the interaction between Fat and Atro, only known binding partner of Fat, I conducted pull-down assays that indicate Fat has multiple binding sites for Atro. However, the interaction is weak, and different experimental conditions will be needed to characterize the interaction. The only known downstream target of both Fat and Atro in PCP is four-jointed. I provided evidence that fjlacZ1.2kb is regulated by the Ecdysone receptor.

Drosophila Fat is a large atypical cadherin molecule. Genetic assays show that Fat has multiple function, however, the mechanism of Fat function is poorly understood. Hence, I undertook a biochemical approach to determine the mechanistic function of Fat. Previous data indicated that Fat might be processed; I further confirmed the precursor-product relationships between these proteins. I then looked at sub cellular localization of Fat. My preliminary data suggests that the smaller 110 kDa forms of Ft goes to the nucleus. To characterize the interaction between Fat and Atro, only known binding partner of Fat, I conducted pull-down assays that indicate Fat has multiple binding sites for Atro. However, the interaction is weak, and different experimental conditions will be needed to characterize the interaction. The only known downstream target of both Fat and Atro in PCP is four-jointed. I provided evidence that fjlacZ1.2kb is regulated by the Ecdysone receptor.

The effects of exercise and dietary intervention on metabolic syndrome (Mets) markers of inactive premenopausal women were investigated. In Study I, early markers of MetS were examined in young, (21.2 ?? 0.3 years), healthy but unfit women (N = 66) consuming a processed food diet. A second aim was to examine the relationship between ethnic influences (European versus Chinese) and early markers of MetS (e.g., hyperinsulinemia). Study II compared the hormonal and metabolic responses to steady state exercise (SSE) and high intensity interval exercise (HIIE) in untrained young women (N = 18, 21.7 ?? 0.8 years). Women were further divided into high and low fasting insulin levels to determine if hyperinsulinemia influenced hormonal and metabolic response to SSE and HIIE. Study III examined the hormonal and metabolic response to a randomized controlled intervention named the Fish oil, Exercise and Mediterranean diet (FEM) trial. The FEM trial was conducted with overweight, inactive young (23.5 ?? 0.6 years) women (N = 56) for 12 weeks. Characteristics of a subset of women (N = 34, 23.5 ?? 0.7 years) in the FEM trial, non-responders (NRES), who did not lose weight (??? 1% loss in mass), were also examined. Metabolic profiles were developed based on body composition, aerobic fitness, blood markers, diet, resting metabolic rate, medical history, blood pressure, and autonomic function. Body composition was measured by skinfolds and girths, bioimpedance (Tanita, Japan), and Dual Energy X-Ray Absorptiometry. Peak oxygen uptake was assessed using an open circuit spirometer, TrueMax 2400 Metabolic Cart. Venepuncture and cannulation techniques were used for collecting blood samples that were also centrifuged and frozen for later analysis. In Study I young women who were physically unfit and consumed a processed food diet possessed high levels of fasting insulin, HOMA-IR (an insulin resistance index), and C-reactive protein (CRP). Insulin, p < .001, and HOMA-IR, p < .05, were significantly greater in Chinese Australians compared to European Australians, whereas plasma CRP levels were significantly, p < .05, lower. Significant differences, p < .05, existed between the groups with the Chinese Australians possessing lower body composition indices. However, ethnic differences still existed for insulin, HOMA-IR, and CRP after adjusting for body composition. Both groups consumed significantly high protein relative to their body mass. Thus, it appears that hyperinsulinemia is one of the earliest markers of MetS in young inactive females of both European and Asian descent who are unfit and consume a high level of dietary protein. In Study II, HIIE compared to SSE proved to be more effective at preventing an increase in insulin levels in the two hours after exercise. Resting respiratory quotient (RQ) was significantly lower, p < .05, following both HIIE and SSE, whereas plasma glycerol levels were higher, p = .06, suggesting greater lipolysis following HIIE. The women were divided by baseline fasting plasma insulin (> 9.98 ??IU/ml) into high insulin (HI) and low insulin groups (LI). The fasting plasma human growth hormone levels of the HI women were significantly lower at baseline compared to that of LI women. Baseline RQ was correlated with baseline glycerol, r = - .54, p < .05. Insulin levels at one hour post HIIE was related to fasting plasma adrenocorticotropic hormone (ACTH) one hour post exercise, r = .52, p < .05. Fasting plasma leptin at one, r = .56, p < .05, and two, r = .53, p < .05, hours post exercise was associated with 2 hour post insulin levels. Interestingly, fasting ACTH was significantly elevated in the 2 hours post exercise in the HI women compared to LI. All diet data between the groups were similar and lipids were in the healthy range with no significant differences between the women possessing high or low fasting plasma insulin. Thus, young women who completed one session of short duration HIIE compared to SSE improved certain aspects of their metabolic profile (e.g., reduced insulin levels) and enhanced their fat oxidation in the immediate two-hour exercise recovery period. Following FEM (a 12-week multi-component lifestyle intervention) overweight women recorded significantly lower, p < .05, body composition (mass, fat mass, percent body fat, waist circumference), insulin, inflammation (CRP), blood pressure, and lipids. The improvements within the Mediterranean diet (Mediet) were related to the reductions in body weight, fat mass, and insulin. Consumption of saturated fats, legumes, meat, poultry, and egg were also significantly decreased, p < .05, following the trial. Adherence to the Mediet and fish oil consumption, measured through a Mediet score, was significantly increased, p < .001, and was associated with reduced levels of fat mass, r = .43, p < .05. Autonomic function (measured by power frequency analysis), aerobic fitness, and fat oxidation were all significantly, p < .05, enhanced. Therefore, an intervention incorporating fish oil consumption, HIIE, and Mediet significantly reduced body fat, fasting insulin, inflammatory markers, and some blood lipids. Interestingly, some women did not lose fat mass following the FEM intervention, despite experiencing significant reductions in insulin, inflammation, waist circumference, blood pressure, and an increase in aerobic power. The major differences between those women who lost fat and those that did not was that the non-responders possessed significantly lower, p < .05, systolic blood pressure, lower resting heart rate, and a higher resting RQ. In summary, in Study I, young, unfit women consuming a processed diet, demonstrated hyperinsulinemia and low grade inflammation. The high levels of fasting insulin suggest that these women are at a higher risk for developing MetS and type 2 diabetes. The results of Study II suggests that one bout of HIIE compared to a longer bout of SSE was more effective at preventing a rise in post-exercise insulin levels. Finally, results of Study III indicate that a 12-week lifestyle intervention, encompassing HIIE, fish oil ingestion, and a Mediet positively influenced early MetS markers (e.g., hyperinsulinemia), aerobic and anaerobic fitness, low grade inflammation, and body composition in young women.

Thesis (M.S.)--Eastern Illinois University, 1992. / Includes bibliographical references (leaves 49-52).