Obesity is a chronic condition that primarily develops from an increase in body fat in the form of white adipose tissue (WAT) mass. The resulting adiposity is a risk factor for many diseases, including type 2 diabetes (T2D), cardiovascular diseases, and some forms of cancer. Reducing WAT mass by targeted modulation of metabolic enzymes in fat cell metabolism is an attractive molecular therapeutic alternative to dietary approaches. In the present study, we exogenously up-regulate a novel respiratory uncoupling protein to increase substrate oxidation, and thereby control adipocyte fatty acid content. Increasing molecular evidence points to a family of uncoupling proteins (UCPs) playing an important role in adipocyte fat metabolism. Of specific interest is UCP1, which in brown adipocytes mediates energy dissipation as heat by de-coupling respiration and ATP synthesis. UCP1 is minimally expressed in white adipose tissue (WAT). We hypothesize that controlled expression of UCP1 in WAT will result in enhanced fatty acid oxidation to compensate for reduced ATP synthesis. We used a Tet-Off retroviral transfection system to express UCP1, with doxycycline being used to control the extent of expression. UCP1 cDNA was cloned into pRevTRE and was stably transfected into 3T3-L1 preadipocytes prior to differentiating them into adipocytes. A reporter gene (EGFP) was also transfected in parallel to optimize the transfection and preadipocyte differentiation conditions as well as to demonstrate regulated expression. Metabolite measurements showed that the UCP1-expressing adipocytes accumulated 83% less triglyceride and 85 % free fatty acids while maintaining constant ATP levels. These results suggest UCP1 and other metabolic enzymes as potential targets for development of pharmacological agents for the treatment of obesity and related disorders.

No description available.

In consideration of the rising prevalence of obesity and its effect on metabolic health and disease, this study was conducted to examine mechanisms involved in adipose tissue function following an acute bout of exercise in abdominal subcutaneous adipose tissue. Sedentary, overweight/obese women (n=10, BMI=30.6±6.0 kg∙m-2, VO2peak=30.3±5.4 mL•kg-1•min-1) completed 2 visits to the lab in which they either exercised for 1 hour or a rested in bed for the equivalent time (control). Experiments were executed randomly using a randomized cross-over study design. Gas exchange measures were measured at three time points before biopsies and subcutaneous adipose biopsies were obtained pre-condition, immediately after condition (0hr), two hours post (2hr), and four hours post (4hr). Acute exercise had significant effects whole body fat oxidation and phosphorylation of insulin signalling proteins, but had no effect on the phosphorylation of proteins regulating the expression of glyceroneogenic genes. In combination, these results suggest that acute exercise can transiently decrease insulin signalling although the mechanism by which this occurs is unclear. Additionally, acute exercise had no effect on the phosphorylation of proteins that are thought to regulate glyceroneogenic gene expression, suggesting that there are either alternative mechanisms involved or that time since the consumption of a meal is a greater stimulus for the activation/upregulation of glyceroneogenesis. Our findings suggest that acute exercise may acutely alter function of adipose tissue such that it contributes to elevations in whole body fatty acid metabolism, however, whether or not chronic adaptations are induced remains an important area for future study. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2013-09-25 20:39:11.506

Background: Green tea is rich in catechin, a polyphenolic antioxidant. Consumption of green tea or extract from green tea has been shown to result in weight loss, increased fat oxidation, and elevated energy expenditure in mice and humans. Green tea consumption has also been shown to result in increased exercise endurance in mice and improved maximal oxygen uptake (VO2max) in humans. It is not clearly known whether green tea consumption would increase exercise endurance in humans. Objective: The aim of this study was to determine if the daily consumption of decaffeinated green tea extract for 4-5 weeks, would improve exercise endurance in humans, as measured by running 2.5 miles on an indoor track. Subjects, Design, and Methods: This study was based on a randomized, double-blind design. Fourteen, normal, healthy individuals volunteered for participation and completed the study. They were divided into two groups (n= 7 for each group). All participants completed 2 endurance trials, 1 at the baseline and 1 at the conclusion of the study. Each trial consisted of a 2.5 mile run around the GSU Recreation Center indoor track. One group consumed green tea extract pill containing 900 mg catechins and the other group consumed a placebo for 4-5 weeks between run trials. Results: Green tea and placebo groups improved their running times, however, there was no significant difference between these two groups in mean end time (P = 0.74). Under one statistical analysis, the green tea group significantly improved their running time compared to baseline (P = 0.019), while the placebo group did not. However, under another statistical analysis (removing one participant due to possible skewing effect), both groups significantly improved their running time over baseline (P< 0.05). Conclusions: This study was not able conclusively ascertain whether or not the daily consumption of green tea improved endurance performance as measured by 2.5 mile run times. Results of this study should be used with caution due to small sample size. Future studies are warranted on the impact of green tea consumption on exercise endurance, using a longer duration and a larger sample size than has been studied.

BACKGROUND: Diaclyglycerol (DAG) oil has the potential as an effective weight control agent as well as an agent to modify overweight related complications. OBJECTIVE: We aim to examine the efficacy of DAG oil (Enova oilTM) on regulating energy expenditure (EE), fat oxidation, body composition, lipid profiles and hepatic lipogenesis in comparison with conventional oils. DESIGN: Twenty-six overweight hypertriglyceridemic women consumed DAG or control oil for 28 days separated by a 4-week washout period using a randomized crossover design. Forty grams of either DAG or control oil were consumed daily by each study subject. RESULTS: DAG oil consumption for a period of 4-week does not alter total EE, fat oxidation, lean mass, fasting lipid profile or fatty acids synthesis rate, but effectively reduces (p<0.05) body weight and adiposity. CONCLUSION: DAG oil maybe an useful agent in the battle against obesity. However, its body weight/composition control effects are not from increasing of lean mass, or postprandial EE and fat oxidation. The consumption of DAG oil for a period of 4-week does not necessarily modify fasting lipid profiles or hepatic lipogenesis to reduce risk of coronary heart diseases in overweight hypertriglyceridemic subjects.

BACKGROUND: Diaclyglycerol (DAG) oil has the potential as an effective weight control agent as well as an agent to modify overweight related complications. OBJECTIVE: We aim to examine the efficacy of DAG oil (Enova oilTM) on regulating energy expenditure (EE), fat oxidation, body composition, lipid profiles and hepatic lipogenesis in comparison with conventional oils. DESIGN: Twenty-six overweight hypertriglyceridemic women consumed DAG or control oil for 28 days separated by a 4-week washout period using a randomized crossover design. Forty grams of either DAG or control oil were consumed daily by each study subject. RESULTS: DAG oil consumption for a period of 4-week does not alter total EE, fat oxidation, lean mass, fasting lipid profile or fatty acids synthesis rate, but effectively reduces (p<0.05) body weight and adiposity. CONCLUSION: DAG oil maybe an useful agent in the battle against obesity. However, its body weight/composition control effects are not from increasing of lean mass, or postprandial EE and fat oxidation. The consumption of DAG oil for a period of 4-week does not necessarily modify fasting lipid profiles or hepatic lipogenesis to reduce risk of coronary heart diseases in overweight hypertriglyceridemic subjects.

Moderate intensity exercise (MIT) was compared to high intensity interval exercise (HIIT) as part of a nine week treatment strategy for 13 obese men. Both groups exercised three days per week beginning at 45% VO2max. The MIT protocol progressed to 65% VO2max by week eight. The HIIT protocol consisting of 16 short (30 s), 8 medium (90 s), and 4 long (180 s) intervals progressed to 110% VO2max, 100% VO2max, and 90% VO2max, respectively, by week nine with low intensity intervals at 40% VO2max. Exercise duration of the MIT group was adjusted to allow for energy expenditure equal to that of the HIIT group. Modest dietary restriction and weekly group nutrition education sessions were part of the treatment. Weight decreased similarly by 2.4% in the MIT group and 2.8% in the HIIT group (p<0.05). For the groups combined, exercise resulted in a 7% decrease in body fat percent (%BF) and a 9% decrease in fat mass (FM) (p<0.05). There was no difference in the change in %BF or FM for either group. There were no changes in fat free mass (FFM) over the treatment or between groups. Waist circumference decreased 2.8% overall with no differences between the two groups (p<0.05). There were no differences in waist-to-hip ratio (WHR) or waist-to-thigh ratio (WTR) due to the intervention. The activity of vastus lateralis b 3-hydroxyacyl CoA dehydrogenase (HADH) increased 37% and 97% (p<0.05) for the MIT and HIIT groups respectively with a trend for differences between the two groups (p=0.055). The results show that an exercise program of moderate or high intensity is effective to cause weight reduction. The data suggest that HIIT may be more effective over a longer treatment period if the observed trend for greater capacity for muscle fat oxidation translates into improved body fat loss. / Master of Science

Identifying the relationship between fat oxidation and insulin resistance (IR) may provide vital clues to the mechanisms behind the development of metabolic disease in prepubertal children. The purpose of this study was to examine the association of fat oxidation with insulin resistance (IR) and insulin sensitivity (SI) in prepubertal children. A total of 34 prepubertal 7-9 year olds (18 females, 16 males, 13 non-Caucasian, 21 Caucasian, 8.0±0.8 years, 36.5±12.1 kg) were observed. Subjects participated in indirect calorimetry to obtain respiratory quotient (RQ) and a blood test to obtain fasting insulin and glucose to calculate IR by homeostatic model assessment (HOMA). A subset (n=16) participated in Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) to obtain insulin sensitivity. Pearson correlations between RQ and IR and RQ and SI were performed. Partial correlations with respect to physical activity, breastfeeding, and birth weight were also performed. A general linear model was used to examine RQ with IR, and separately SI with respect to physical activity, breastfeeding, birth weight, race and sex. Respiratory quotient and IR were significantly associated when adjusted for physical activity, sex and race and breastfeeding, sex and race. In regards to birth weight, RQ and IR were significantly associated when adjusted for breastfeeding, birth weight, and race, but not when breastfeeding was removed from the model. The results of this study suggest lack of physical activity and breastfeeding may be the most influential risk for factors in the development of IR via a mechanism of impaired fat oxidation. Further research is needed to examine the role of physical activity, breastfeeding, and birth weight on fat oxidation and the development of insulin resistance in prepubertal children, however, the results of this study support the promotion of physical activity, breastfeeding, and good maternal nutrition.

L'arthrite juvénile idiopathique (AJI) est une maladie rare chronique caractérisée par une inflammation persistante qui se manifeste par des douleurs articulaires, le gonflement des articulations et la limitation des mouvements articulaires. La fatigue et les douleurs entraînent une diminution de l'activité physique et une sédentarité accrue. Ce manque d'activité physique a pour conséquence une altération de la qualité de vie et une aggravation de la fatigue chronique, des troubles de l'humeur et des troubles métaboliques chez ces enfants. Les études sur les programmes d'exercices physiques montrent que l'exercice physique est bénéfique pour cette population. Mais les mécanismes d’action permettant de comprendre comment elle améliore la qualité de vie et la santé de l'enfant atteint d'arthrite juvénile idiopathique sont encore mal connus. Notre objectif était d’explorer la réponse physiologique à l’exercice des enfants et adolescents atteints d’arthrites juvéniles idiopathiques. Nous nous sommes intéressés principalement au métabolisme énergétique à l’exercice et à la fonction musculaire chez ces enfants. Nous avons étudié l’impact de la pathologie, des traitements par anti-TNF-α et de l’activité de la maladie sur ce métabolisme. Ensuite, nous avons étudié la sécrétion induite par l’exercice des myokines telles que l’IL-6 et les calgranulines en post exercice immédiat et dans les 24h suivant l’exercice. / Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disease characterized by persistent inflammation that is manifested by joint pain, swelling of the joints and limitation of range of motion. Fatigue and pain are the most frequent complaints in patients with JIA, lead to a decline in physical activity and a sedentary lifestyle of these children. This lack of physical activity results in impaired quality of life and worsening of chronic fatigue, mood disorders and metabolic disorders in these children. Studies of exercise programs show that exercise is beneficial for this population. But the mechanisms of action to understand how it improves the quality of life and health of children with juvenile idiopathic arthritis are still poorly understood. Our aim was to explore the physiological response to exercise in children and adolescents with juvenile idiopathic arthritis. We focused primarily on energy metabolism to exercise and muscle function in these children. We looked at the impact of the pathology, anti-TNF-α treatments and the activity of the disease on this metabolism. Next, we adressed the exercise-induced secretion of myokines such as IL-6 and calgranulins in immediate post exercise and within 24 hours after exercise.

Hintergrund: Ein Training bei absolut maximalem Fettumsatz ist interessant für Patienten, gesundheitsorientierte Freizeitsportler und leistungsorientierte Sportler. Der klassische Laktat-Laufband-Stufentest erlaubt keine direkten Schlüsse auf den Fettumsatz. Methoden: Es wurde ein modifizierter ergospirometrischer Laufband-Stufentest entwickelt, der eine 30 minütige Einlaufphase bei sehr geringer Intensität besitzt. In der darauf folgenden Auswertungsphase wurde alle 3 min die Geschwindigkeit um 0,2 m/s pro Stufe erhöht. Wegen des Anstieges des Fettumsatzes mit zunehmender Laufdauer wurden in der Auswertungsphase die berechneten Fettumsätze um 2,5 mg/min reduziert, um eine bessere Vergleichbarkeit der Stufen zu gewährleisten. Dieser neu entwickelte Test wurde anschließend mit einem klassischen Laktat-Laufband-Stufentest verglichen. Ergebnisse: Die Herzfrequenzen bei Laktat 2 mmol/l liegen intraindividuell betrachtet im Median um 16 bpm höher als die bei absolut maximalem Fettumsatz. Einen Trainingsbereich für die absolut maximale Fettverbrennung gibt man möglichst an, indem man den Herzfrequenzbereich zwischen Über- und Unterschreiten von 90 % des absolut maximalen Fettumsatzes definiert. Dieser hat im Median eine Breite von 27 bpm und reicht im Median von 125 bpm bis 151 bpm. Der absolute maximale Fettumsatz beträgt im Median 432 mg/min. Bei den Herzfrequenzen von Laktat 2 mmol/l, erstem Laktatanstieg bzw. einer um 15 bpm reduzierten Herzfrequenz von Laktat 2 mmol/l, betragen die Fettumsätze 86 %, 96 % bzw. 97 % des absolut maximalen Fettumsatzes. Der Anteil der Fette beträgt bei absolut maximalem Fettumsatz im Median 51 % am Gesamtenergieumsatz. Der Laktatspiegel bei absolut maximalem Fettumsatz beträgt im Median 1,4 mmol/l. Die Intensität bei absolut maximalem Fettumsatz entspricht im Median 66 % der maximal möglichen Sauerstoffaufnahme.