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These studies determined the role of carbohydrate deficit from acute exercise on postprandial triglyceride elevation (PPTG). In Study 1, when energy expenditure was held constant in the exercise trials, both acute moderate (~50% VO₂ peak; MIE) and high intensity endurance exercise (90% VO₂ peak intervals; HIE) were effective to lower PPTG compared to a non-exercise control [CON; 54.9 (13.5) % and 75.2 (15.5) %, respectively, relative to CON, p<0.05], with HIE significantly lower than MIE (p=0.03). Total postprandial fat oxidation was increased in both MIE [83.3 (10.6) %] and HIE [89.1 (9.8) %] compared to CON [69.0 (16.1) %, p<0.05), with HIE significantly greater then MIE (p=0.012). These effects occurred in the absence of any change in glucose tolerance. In Study 2, when an isoenergetic meal was provided immediately after an acute exercise session (80 min; 60 min at ~65% VO₂peak and 10, 2 min intervals) consisting of either low carbohydrate (EX+LCHO) or high carbohydrate content (EX+HCHO), PPTG was siginificantly higher in EX+HCHO compared to EX+LCHO [449 (118) mg/dL/4h and 325 (63) mg/dL/4h, respectively, p=0.03], despite similar energy balance. Furthermore, postprandial fat oxidation was higher in EX+LCHO compared to EX+HCHO [256.7 (57.6) kcal/4h and 209.4 (56) kcal/4h, respectively, p=0.002]. PPTG was significantly related to fat oxidation (r=-0.61), fasting plasma [beta]-hydroxybutyrate (r=-0.62) and carbohydrate deficit (r=0.51), but not energy deficit (r=0.25). In summary, these data suggest that post-exercise carbohydrate balance from both increasing carbohydrate oxidation during exercise (i.e., exercise intensity) or by reducing post-exercise carbohydrate intake, is an important determinant of PPTG-lowering effects of exercise and that this may result from changes in fat oxidation. / text

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No description available.

Postprandial overproduction of apolipoprotein B48 (apoB48)-containing lipoproteins has been observed in states of insulin resistance and is important to the sequelae of cardiovascular disease, but little is understood about factors that regulate their secretion. The glucagon-like peptides (GLPs) are released from ileal enteroendocrine L-cells following lipid ingestion. I hypothesized that the GLPs could acutely affect the production of apoB48-containing triglyceride (TG)-rich lipoproteins (TRL) in the small intestine. Using the Syrian golden hamster, I first characterized the gross effects of the GLPs on TRL secretion in response to an oral fat load and then continued to dissect the mechanisms of these changes using primary intestinal cell cultures and a variety of knockout mouse models. An exogenous GLP-1 receptor (GLP-1R) agonist was found to acutely inhibit chylomicron secretion in both hamsters and mouse models, and extending the bioactivity of endogenously-secreted GLP-1 with a dipeptidyl peptidase-4 inhibitor had suppressive effects in insulin-resistant fructose-fed hamsters. The insulinotropic and delayed gastric emptying functions do not completely account for the hypolipidemic effect of GLP-1R agonism, and the effect of the GLP-1R agonist exendin-4 could be seen directly in the apoB48 secretion of primary enterocytes. In contrast, the sister peptide GLP-2 was a potent acute stimulator of chylomicron secretion in hamsters and mice. The hyperlipidemic effect of GLP-2 could be attributed to an increased rate of luminal FA uptake mediated by the posttranslational modification of the FA transporter CD36, and CD36-deficient mice were found to be refractory to the stimulatory effects of GLP-2. The activity of nitric oxide synthase was also found to be essential to the hyperlipidemic action of GLP-2. I identified a set of intercellular communications that could contribute in mediating the action of GLP-2, in which GLP-2 secreted from the enteroendocrine L-cell stimulates intestinal subepithelial myofibroblasts to release vascular endothelial growth factor, which directly activated the enterocyte to secrete apoB48. In summary, this thesis demonstrates that two co-secreted postprandial hormones have considerable but completely opposite influences on chylomicron production. Changing the balance of the GLPs’ actions in vivo could provide a therapeutic strategy to combat postprandial dyslipidemia.

Postprandial overproduction of apolipoprotein B48 (apoB48)-containing lipoproteins has been observed in states of insulin resistance and is important to the sequelae of cardiovascular disease, but little is understood about factors that regulate their secretion. The glucagon-like peptides (GLPs) are released from ileal enteroendocrine L-cells following lipid ingestion. I hypothesized that the GLPs could acutely affect the production of apoB48-containing triglyceride (TG)-rich lipoproteins (TRL) in the small intestine. Using the Syrian golden hamster, I first characterized the gross effects of the GLPs on TRL secretion in response to an oral fat load and then continued to dissect the mechanisms of these changes using primary intestinal cell cultures and a variety of knockout mouse models. An exogenous GLP-1 receptor (GLP-1R) agonist was found to acutely inhibit chylomicron secretion in both hamsters and mouse models, and extending the bioactivity of endogenously-secreted GLP-1 with a dipeptidyl peptidase-4 inhibitor had suppressive effects in insulin-resistant fructose-fed hamsters. The insulinotropic and delayed gastric emptying functions do not completely account for the hypolipidemic effect of GLP-1R agonism, and the effect of the GLP-1R agonist exendin-4 could be seen directly in the apoB48 secretion of primary enterocytes. In contrast, the sister peptide GLP-2 was a potent acute stimulator of chylomicron secretion in hamsters and mice. The hyperlipidemic effect of GLP-2 could be attributed to an increased rate of luminal FA uptake mediated by the posttranslational modification of the FA transporter CD36, and CD36-deficient mice were found to be refractory to the stimulatory effects of GLP-2. The activity of nitric oxide synthase was also found to be essential to the hyperlipidemic action of GLP-2. I identified a set of intercellular communications that could contribute in mediating the action of GLP-2, in which GLP-2 secreted from the enteroendocrine L-cell stimulates intestinal subepithelial myofibroblasts to release vascular endothelial growth factor, which directly activated the enterocyte to secrete apoB48. In summary, this thesis demonstrates that two co-secreted postprandial hormones have considerable but completely opposite influences on chylomicron production. Changing the balance of the GLPs’ actions in vivo could provide a therapeutic strategy to combat postprandial dyslipidemia.

abstract: Objective: Vinegar consumption studies have demonstrated possible therapeutic effects in reducing HbA1c and postprandial glycemia. The purpose of the study was to closely examine the effects of a commercial vinegar drink on daily fluctuations in fasting glucose concentrations and postprandial glycemia, and on HbA1c, in individuals at risk for Type 2 Diabetes Mellitus (T2D). Design: Thirteen women and one man (21-62 y; mean, 46.0&plusmn;3.9 y) participated in this 12-week parallel-arm trial. Participants were recruited from a campus community and were healthy and not diabetic by self-report. Participants were not prescribed oral hypoglycemic medications or insulin; other medications were allowed if use was stable for > 3 months. Subjects were randomized to one of two groups: VIN (8 ounces vinegar drink providing 1.5 g acetic acid) or CON (1 vinegar pill providing 0.04 g acetic acid). Treatments were taken twice daily immediately prior to the lunch and dinner meals. Venous blood samples were drawn at trial weeks 0 and 12 to measure insulin, fasting glucose, and HbA1c. Subjects recorded fasting glucose and 2-h postprandial glycemia concentrations daily using a glucometer. Results: The VIN group showed significant reductions in fasting capillary blood glucose concentrations (p=0.05) that were immediate and sustained throughout the duration of the study. The VIN group had reductions in 2-h postprandial glucose (mean change of &minus;7.6&plusmn;6.8 mg/dL over the 12-week trial), but this value was not significantly different than that for the CON group (mean change of 3.3&plusmn;5.3 mg/dL over the 12-week trial, p=0.232). HbA1c did not significantly change (p=0.702), but the reduction in HbA1c in the VIN group, &minus;0.14&plusmn;0.1%, may have physiological relevance. Conclusions: Significant reductions in HbA1c were not observed after daily consumption of a vinegar drink containing 1.5 g acetic acid in non-diabetic individuals. However, the vinegar drink did significantly reduce fasting capillary blood glucose concentrations in these individuals as compared to a vinegar pill containing 0.04 g acetic acid. These results support a therapeutic effect for vinegar in T2D prevention and progression, specifically in high-risk populations. / Dissertation/Thesis / M.S. Nutrition 2013

abstract: In adults, consuming a high-fat meal can induce endothelial dysfunction while exercise may mitigate postprandial endothelial dysfunction. Whether exercise is protective against postprandial endothelial dysfunction in obese youth is unknown. The purpose of this study was to determine if high-intensity interval exercise (HIIE) performed the evening prior to a high-fat meal protects against postprandial endothelial dysfunction in obese adolescent males. Fourteen obese adolescent males (BMI%tile=98.5±0.6; 14.3±1.0yrs) completed the study. After initial screening, participants arrived, fasted at 9:00 in the morning where brachial artery flow-mediated dilation (FMD) was measured using duplex ultrasound after 20min of supine rest (7.0±3.0%) and completed a maximal exercise test on a cycle ergometer (VO2peak=2.6±0.5 L/min). Participants were randomized and completed 2 conditions: a morning high-fat meal challenge with evening prior HIIE (EX+M) or a morning high-fat meal challenge without prior exercise (MO). The EX+M condition included a single HIIE session on a cycle ergometer (8 X 2min at &#8805;90%HRmax, with 2min active recovery between bouts, 42min total) which was performed at 17:00 the evening prior to the meal challenge. In both conditions, a mixed-meal was tailored to participants body weight consisting of 0.7g of fat/kg of body weight consumed (889±95kcal; 65% Fat, 30% CHO). FMD was measured at fasting (>10hrs) and subsequently measured at 2hr and 4hr after high-fat meal consumption. Exercise did not improve fasting FMD (7.5±3.0 vs. 7.4±2.8%, P=0.927; EX+M and MO, respectively). Despite consuming a high-fat meal, FMD was not reduced at 2hr (8.4±3.4 vs. 7.6±3.9%; EX+M and MO, respectively) or 4hr (8.8±3.9 vs. 8.6±4.0%; EX+M and MO, respectively) in either condition and no differences were observed between condition (p(condition*time)=0.928). These observations remained after adjusting for baseline artery diameter and shear rate. We observed that HIIE, the evening prior, had no effect on fasting or postprandial endothelial function when compared with a meal only condition. Future research should examine whether exercise training may be able to improve postprandial endothelial function rather than a single acute bout in obese youth. / Dissertation/Thesis / Ph.D. Exercise and Wellness 2014

Coronary Heart Disease (CETO) is one of the most common causes of mortality in industrialised societies, and it has been demonstrated elsewhere that shift workers have an increased risk of developing CHD compared to day-workers. One possible explanation for this increased risk is that a shift worker may show inappropriate postprandial responses to a night-time meal, when their biological clock is not adapted to the night shift. This could lead to an elevation in the circulating levels of certain hormones and metabolites, such as triacylglycerol (TAG) and insulin, which are known to be risk factors for CHD. This thesis investigated the relationships between meal times and postprandial hormone and metabolic responses in simulated and real-life shift-workers. The work is presented as three major clinical trials. In the first of these, a combination of timed bright light and darkness/sleep was used to induce a gradual 9-hour phase advance in 12 healthy subjects, who then underwent a rapid 9-hour phase delay. Three meal study days were arranged, to occur during the baseline condition, immediately after the rapid phase delay, so that the subjects effectively had "simulated jet lag", and two days later. Blood parameters measured included plasma glucose, insulin, proinsulin, C-peptide, non-esterified fatty acids (NEFA), TAG and glucose- dependent insulinotropic polypeptide (GIP). Substantial differences in plasma TAG and NEFA were observed in the postprandial responses when the subjects consumed an identical meal immediately after the rapid phase delay, compared with during the baseline conditions. Two days after the rapid phase delay, subjects showed inteimediate hormone and metabolite levels, suggesting that the biological clock had a major effect on these postprandial responses. In the second study, day and night-time postprandial responses were compared in a simulated shift work environment, and the effectiveness of a number of potentially beneficial procedures was investigated. These included alterations to the content of the meal consiraied prior to the night shift, bright light exposure during the night shift, and a daytime rest period prior to the night shift. As in the first study, significant differences were seen in a number of hormones and metabolites on the night shift. compared with during the day. The content of the previous meal, bright light exposure and a daytime rest period prior to the night shift all had significant effects on the night-time postprandial responses. The most exciting discovery made was that a single 8-hour night-time bright light exposure significantly lowered the TAG postprandial responses on the simulated night shift. As all the work conducted up until this point had utilised simulated conditions, it was important to illustrate that similar differences in postprandial responses at night-time could be demonstrated in "real-life shift workers". Thus, nine midwives were recruited from the Royal Surrey County Hospital, and studied on four occasions. This allowed comparison of postprandial responses on both day and night shifts, and also allowed further investigation of the effect of altering the content of the previous meal. Significant differences were again found in a number of blood parameters when the night-time and day-time responses to the test meal were compared, with the most striking being a delayed NEFA rise on the night shift, compared with during the day. In conclusion, this series of studies have illustrated that the human body responds differently to a meal consumed at night-time, compared with during the day, both in a simulated and a real-life environment. This results in variations in the levels of a number of known CHD risk factors, and may be linked with the elevated CHD risk reported in shift workers. Alteration to the meal prior to the night shift, exposure to bright light during the night shift, and instituting a rest period prior to the night shift, were all shown to be potentially beneficial in reducing the variation between day and night-time responses.