Master of Science / Department of Human Nutrition / Sara K. Rosenkranz / Background: High-fat meals (HFM) have been shown to increase postprandial lipemia (PPL) and inflammation. Acute exercise both pre and post-meal has been shown to attenuate PPL and inflammation. However, studies examining the interaction of HFMs and exercise on PPL and inflammation have used meal and exercise conditions more extreme than typical for average adults. The purpose of this study was to determine if moderate intensity exercise following a "true-to-life" HFM would attenuate PPL and inflammation. Methods: Participants were thirty-nine young adults (18-40 years) with no known metabolic disease. Inclusion criteria consisted of participants meeting physical activity guidelines of ≥ 150 min/week of moderate-to-vigorous physical activity or ≥ 75 min/week of vigorous activity, or < 30 min of planned physical activity per week. Participants were block randomized to EX or CON groups. Participants consumed a HFM of 10 kcal/kgbw. The EX group walked at 60% VO[subscript 2peak] to expend ≈ 5 kcal/kgbw beginning one-hour following the HFM. The CON group remained sedentary during the postprandial period. Blood samples were collected at baseline and 2, and 4hrs postprandially. Results: At baseline, there were no differences between EX and CON groups for any metabolic or inflammatory markers (p>0.05). Postprandial TRG increased ≈ 100% (p<0.001) in both groups, with no differences between groups. HDL concentrations decreased across time in both groups (p<0.001) with no differences between groups (p=0.338). HDL was higher in the EX group at 2hrs (p=0.047), but not 4hrs (p=0.135). IL-6 and TNF-α concentrations did not change over time with no differences between groups (p>0.05). The EX group increased sVCAM-1 from baseline to 4hr (p=0.003), while the CON group did not. Change in TRG was associated with change IL-6, IL-8, IL-10 and TNF-α from baseline to 2hrs when controlling for VO[subscript 2peak] and body fat%. No other associations were seen between change scores for TRG and inflammatory markers. Conclusions: Despite significant increases in PPL following a HFM, moderate intensity exercise in the postprandial period did not mitigate the PPL nor the inflammatory response to the HFM. These results indicate PPL and inflammation following a HFM are not directly related in a young, healthy population with low metabolic risk.

Sirtuins (SIRT) regulate the transcription of various genes involved in the development of diet-induced obesity and chronic disease; however, it is unknown how they change acutely following a high-fat meal. The purpose of this study was to determine the effect of a high-fat meal (65% kcals/d; 85% fat recommendation), on SIRT1-7 mRNA expression in blood leukocytes at 1, 3, and 5-h post-prandial. Men and women (N=24) reported to the lab following an overnight fast (>12H). Total RNA was isolated and reverse transcribed prior to using a Taqman qPCR technique with 18S rRNA as a normalizer to determine SIRT1-7 mRNA expression. An additional aliquot of serum was used to measure triglycerides. Data was analyzed using a RM ANOVA with P<0.05. Triglycerides (P<0.001; 124%) peaked at 3-h. SIRT 1 (P=0.004; 70%), and SIRT 6 (P=0.017; 53%) decreased expression at 3-h. SIRT4 (P=0.024) peaked at 5H relative to baseline (70%) and 3-h (68%). To our knowledge, this is the first study to report that consumption of a high-fat meal transiently alters SIRT mRNA expression consistent in a pattern that mirrors changes in serum triglycerides. Decrease in expression of SIRT1 and SIRT6 combined with an increased SIRT4 would be consistent with an increase in metabolic disease risk if maintained on a chronic basis.

Doctor of Philosophy / Department of Kinesiology / Craig A. Harms / The overall aim of this dissertation was to determine the impact of lifestyle (i.e. habitual and acute physical activity and diet), age, and sex on systemic and airway inflammation and oxidative stress. In study 1 (Chapter 2) we examined the impact of habitual physical activity level on the post-prandial airway inflammatory response following an acute bout of moderate intensity exercise. Results indicated that the mean exhaled nitric oxide (eNO; marker of airway inflammation) response increased for all groups at two hours post high-fat meal (HFM) (~6%) and returned to baseline by four hours post-HFM. However, there was a varying eNO response from baseline to four hours in the group that exercised in the post-prandial period compared to the group that remained sedentary. These findings suggest airway inflammation occurs after a HFM when exercise is performed in the post-prandial period, regardless of habitual physical activity level. In study 2 (Chapter 3) we investigated the post-prandial oxidative stress response to meals of varying calories and fat. Specifically, we assessed the post-prandial airway and systemic 8-isoprostane (a marker of oxidative stress) responses to meals with moderate-fat (8.5 kcal/kg of bodyweight) and high-fat content (17 kcal/kg of bodyweight) from baseline to six hours post-meal in a randomized crossover design. This study revealed that systemic 8-isoprostane increased from baseline to six hours post-meal (38.3%), but there was no difference between the moderate-fat meal (MFM) and HFM conditions. There were no changes in airway 8-isoprostane from baseline to six hours post-MFM or HFM, or between the MFM and HFM conditions. Lastly, in study 3 (Chapter 4), we were interested in examining 8-isoprostane responses in older adults, since 8-isoprostane has been reported to increase with age. Previous research also suggests that older women (OW) and older men (OM) have differences with regard to prevalence and severity of late-onset asthma. In this study, we sought to determine whether the airway 8-isoprostane response to a strenuous bout of exercise was different in OW compared to OM. A secondary aim was to determine whether post-exercise 8-isoprostane generation was correlated with decrements in lung function. Our results showed that the generation of 8-isoprostane from pre- to post-exercise increased ~74±77% in OW and decreased ~12±50% in OM. The decrease in 8-isoprostane generation was not correlated with improvements in lung function from pre- to post-exercise. These findings collectively contribute to the literature by enhancing our understanding of the impact of lifestyle factors, age and sex on modifying and potentially mitigating the risk of developing chronic diseases.

Peripheral blood mononuclear cells (PBMCs) can respond to dietary stimuli modulating the up-regulation of pro-inflammatory cell signaling, which is associated with metabolic disease and has been seen to be elevated in African American (AA) when compared to Caucasian American (CA) women. Little is known about the response of PBMCs to a high fat meal among women and the potential impact of ethnicity and/or weight status on this response. The purpose of this study was to examine PBMC response to consuming a high fat meal and the response to culturing PBMCs in media supplemented with lipid among AA and CA women, and to determine the impact that ethnicity and/or weight status may have on this response. Twenty-one women participated in the study: 10 AA (age: 28.00±6.60), 11 CA (age: 26.91±6.28), of whom 11 were lean (BMI

Thesis (M.Sc. (Chemical Pathology)) --University of Limpopo, 2013 / Objectives The present study investigated how the serum lipids responded to a high-fat meal in black South African subjects with different APOE genotypes, a population that until recently was reported to be consuming a traditional diet of low fat and high carbohydrates. Methods Sixty students (males and females) of the University of Limpopo, Turfloop Campus were successfully genotyped using Restriction Fragment Length Polymorphism (RFLP) and grouped into four APOE genotype groups; ε2, ε2/ε4, ε3 and ε4. Only thirty-three subjects volunteered to participate in the oral fat-tolerance test (OFTT), but two were excluded for having abnormal total cholesterol (6.05 mmol/l) and LDL cholesterol (3.12 mmol/l) so only 31 subjects were left. The numbers per group were ε2=5, ε2/ε4=8, ε3=9 and ε4=9. After an overnight fast blood was drawn for measurements of baseline serum parameters. Subjects were administered a high fat meal 30 minutes after the baseline blood sample was drawn. Blood was drawn at intervals of 20, 40, 60, 120, 180, 240, 300 and 360 minutes for measurements of postprandial serum parameter levels. Serum parameters measured were triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, glucose and insulin. Results Mean levels of serum lipids at baseline in mmol/l were as follows; group 1[TG=0.69(0.55-0.81), TCHOL=3.10±0.29, HDL-C=1.12±0.32, LDLC= 1.67±0.28]; group 2 [TG=0.61(0.53-1.00), TCHOL=2.98±0.53, HDLC= 1.20±0.37, LDL-C=1.43±0.37]; group 3 [TG=0.67(0.28-0.86), TCHOL=2.96±0.54, HDL-C=1.22±0.30, LDL-C=1.46±0.47]; group 4 [TG=0.76(0.51-1.16), TCHOL=3.27±0.51, HDL-C=1.12±0.17, LDLC= 1.79±0.47]. There was no significant difference in the mean levels of baseline triglyceride, total cholesterol, low density lipoprotein cholesterol, and ix high density lipoprotein cholesterol between the APOE groups hence no significant difference in the response to a fatty meal. Conclusions There was no significant change in serum lipid concentrations after a fatty meal in individuals with different APOE genotypes in a population that consume a traditional diet of low fat and high carbohydrates. Due to the small sample size, the results should be interpreted with caution. A larger study is recommended to ascertain the role of APOE genotypes on serum lipid response to a fatty meal in Black South African population.

This study investigated the effects of daily consumption of Thompson seedless raisins on markers of inflammation, oxidative stress and endothelial activation in response to an acute high-fat meal in obese individuals. Seventeen overweight men and women consumed raisins or placebo (264 kcal/d) for 14 d in a randomized cross-over design while following a low-flavonoid, weight-maintenance diet. Four high-fat (53% fat) meals were consumed with the respective treatment pre and post interventions. Measures at fasting, and 2, 3 and 4 hours postprandial included markers of oxidative stress (urinary 8-isoPGF2α; serum Oxygen Radical Absorbance Capacity, ORAC), inflammation (serum C-reactive protein, CRP; interleukin-6, IL-6), endothelial function (serum soluble intercellular adhesion molecule-1, sICAM-1; soluble vascular adhesion molecule-1, sVCAM-1), and metabolic measures (free fatty acids (FFA), triacylglycerol (TAC), glucose, insulin). Urinary 8-isoPGF2α decreased 22% and ORAC increased 3% pre to post interventions combined. Postprandial metabolic responses differed by gender, males surpassed females for several measures: FFA, triacylglycerol, glucose, and sVCAM-1. Neither the meals nor treatment with raisins had any noteworthy influence on fasted measures of inflammation or endothelial dysfunction. Acute high fat meal consumption did not result in evidence of inflammation or oxidative stress in these relatively healthy, overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress. Gender influenced metabolic responses to meals; males had a greater postprandial response in metabolic measures than females. / Master of Science

It is well established that continual consumption of a diet high in fat leads to the development of chronic conditions such as obesity, cardio metabolic syndrome, and atherosclerosis that are associated with high incidence of cardiovascular disease. Recent studies have identified endotoxin-derived inflammation as a major diving force for the development of these conditions. Our laboratory has recently demonstrated that consumption of a single high-fat meal results in acute postprandial endotoxemia and alters monocyte cell surface adhesion molecule expression and scavenger receptor CD36 expression. These collective projects describe our efforts to understand the physiological significance of these postprandial changes and if supplementation with spore-based probiotics are able to provide any form of protection against these responses that are associated with the onset of atherogenesis.