Vitamins are readily available in the modern diet due to liberalized fortification and supplementation policies. This research tested the hypothesis that high multi-vitamin intake by Wistar rats during pregnancy leads to the development of obesity and characteristics of the metabolic syndrome in the offspring. Pregnant Wistar rats were fed the AIN-93G diet containing either the recommended (RV) or 10-fold increase (HV) in vitamin content. Pups were weaned to the RV diet (Study 1), an obesogenic liquid diet (Ob, Study 2), low vitamin diets (1/3RV or 1/6RV, Study 3), or a nutrient selection paradigm (NSP) with 10% and 60% casein diets (Study 4). Body weight (BW), food intake (FI), glucose and insulin responses, appetite hormones, abdominal fat pad mass (FPM) and systolic blood pressure (SBP) was measured. Expressions of mRNA for hypothalamic serotonin (5-HT) receptors and proopiomelanocortin (POMC) were measured in Study 4. Males, but not females, born to HV dams had higher post-weaning BW and FI when weaned to the RV or 1/3RV diet, and exhibited components of metabolic syndrome, including higher FPM, hyperglycemia, insulin resistance and elevated SBP compared with those born to RV dams. The Ob diet led to exaggerated weight gain and expressions of components of metabolic syndrome in both sexes born to dams fed the HV diet. Female pups on the 1/6RV diet from HV dams had two-fold higher glucose response and lower insulin response, but no difference in post-weaning BW and daily FI compared to those from RV dams. In contrast to the pups born to HV dams and fed a single diet, those from the HV dams and on the NSP gained less weight and ate less, and had lower hypothalamic mRNA expressions of 5-HT receptors and POMC. In conclusion, high multi-vitamin intake during pregnancy may lead to obesity, and result in a higher risk of developing characteristics of metabolic syndrome in the offspring. However, sex, weaning diet composition, and the presence of diet choice alter the outcomes.

The hypothesis that source of protein in a nutritionally adequate diet during gestation, lactation and weaning alters food intake and characteristics of metabolic syndrome in the offspring was investigated. Pregnant Wistar rats were randomized to either the AIN 93-G casein (C) or soy protein (S) diets (n=12/group) during gestation only or during gestation and lactation. Male offspring in each dams’ diet group were weaned to either C or S diets (n=12/group). Food intake, body weight (BW), fat pad mass, systolic (SBP) and diastolic (DBP) blood pressure, and plasma homocysteine (p<0.05) were higher in offspring born to dams fed the S diet. Fasting blood glucose (BG), BG in response to a glucose gavage and Homeostatic Model of Assessment of Insulin Resistance (HOMA-IR) index were higher only in male offspring born to dams fed the S diet. Moreover, gene expression of Agouti Related Protein (AgRP) was higher in offspring born to dams fed the S diet at weaning. Extending the dams’ diet during gestation and lactation magnified the effect of the gestational S diet on BW and composition and glucose metabolism in male offspring. Although composition of the weaning diets interacted with that of the dams’ diets, the latter was the dominant factor in determining metabolic outcomes in the offspring. In conclusion, the soy protein diet, compared to the casein diet when consumed during gestation or throughout gestation and lactation increased food intake and the presence of characteristics of metabolic syndrome in the offspring.

Significance: Morbidity and mortality related to CVD among women in the U.S. and most developed countries surpasses that of all cancers combined (AHA, 2008). Yet, CVD in women remains understudied, yielding low awareness among women and healthcare providers. The purpose of this study was to examine whether the relationship between health beliefs related to perceived cardiovascular disease (CVD) severity and health promoting behaviors were different in women with high self perception of CVD susceptibility versus women with low self perception of CVD susceptibility. Methods: This study used a descriptive, correlational design. A convenience sample (N = 220) included female registered nurses (RNs), 23-66 years old (M = 48; SD = 9.7), mostly white (N = 143; 65%), who had worked in nursing an average of 21 years (SD = 11.3) and reported their job as stressful/very stressful (N = 129; 59%). Nurses were recruited from five acute care hospital systems in a large southeastern city. Data were collected using standard questionnaires that measured perceived CVD severity and susceptibility, social support, depression, stress, exercise and nutrition. Participants completed data collection via an online survey method. Results: Data were analyzed using MANCOVA. For every standardized unit increase in perceived severity of CVD, participants had a 1.26 (95% CI: 0.02, 2.50) unit reduction in their healthy food choice score (lower scores = healthier food choices), and a 0.12 increase in their physical activity score (higher scores = more physical activity) (90% CI: 0.01, 0.23) unit. For every standardized unit increase in perceived CVD susceptibility there was an increase in the healthy food choice score by 2.37 (95% CI: 1.09, 3.65) units, and a reduction in the physical activity score by 0.27 (95% CI: 0.12, 0.41) unit. Greater age (p = 0.01) and greater depression (p = 0.001) were statistically significant predictors of lower physical activity. CVD susceptibility did not moderate the effect of CVD severity on nutrition or physical activity. Conclusions: Higher perceived CVD severity was associated with increased likelihood for healthy food choices and physical activity. In contrast, higher perceived CVD susceptibility was associated with decreased likelihood for healthy food choices and physical activity. More research is needed to understand how susceptibility beliefs around CVD are formed in women and how to better engage women in risk reduction behavior.

Background: Breast and Gynecological cancers are a major public health problem. Smoking is associated with several chronic diseases including cancer. Other lifestyles of public health predispose many people to dyslipidemia, hypertension and obesity; risk factors for metabolic syndrome, and are associated with cancer. Objectives: The purpose of this study is to find if those who smoke, and have the metabolic syndrome, are more likely to have breast or gynecological cancers, and to find the distribution by education, having health insurance, race/ethnicity and socio-economic status. Methods: A case-control study of females aged 20 years and above who participated in the United States National Health and Nutrition Examination Survey (NHANES) 2001-2010. Results: Females who have smoked more than hundred cigarettes in life and still smoke; a) have a 42 percent less chance of having a breast cancer diagnosis (OR 0.58; 95% CI 0.36 – 0.93, p-value 0.025), and b) are 2.67 times as likely to report a cervical cancer diagnosis as females who have smoked less than hundred cigarettes in life (OR 2.67; 95% CI 1.72 – 4.13, p-value Conclusion: Smoking and metabolic syndrome are very important indicators of reproductive health and needs further study. Smoking cessation interventions should be an integral part of cervical cancer prevention programs especially targeted at younger females and females who live below the federal poverty level.

This thesis evaluated supplementation with two components of flaxseed during exercise training on inflammation in older adults.<P>Experiment 1: This experiment assessed secoisolariciresinol diglucoside (SDG) supplementation during aerobic exercise training on inflammation in older adults. Methods: One hundred subjects aged 50y or older were randomized to receive either SDG or placebo before completing a 6-month walking program. Fasting concentrations of interleukin-6 and tumor necrosis factor-á, glucose, triacylglycerol (TAG), high density lipoprotein (HDL), low density lipoprotein, and total cholesterol as well as leukocyte cell count were measured every two months while body composition, resting blood pressure, and a composite Z-score of six metabolic syndrome risk factors were assessed at baseline and 6 months. Results: Men on placebo increased metabolic syndrome composite Z-score (p<0.05). TAG increased (p=0.017) in men on placebo relative to men on SDG and men on SDG decreased (p=0.045) DBP relative to men on placebo. Conclusions: SDG had no effect on inflammation while it is effective in attenuating risk factors associated with metabolic syndrome in older males but not females.<p>Experiment 2: This experiment evaluated alpha-linolenic acid (ALA) supplementation during strength exercise training on inflammation in older adults. Methods: Fifty-one healthy older adults (65.4±0.8y) were randomized to receive ALA or a placebo before completing a 12 wk strength training program. Subjects were evaluated at baseline and 12 weeks for TNF-á and IL-6, muscle strength, body composition, and muscle thickness. Results: Males supplementing with ALA decreased IL-6 concentration (p=0.003). The female placebo and male ALA group had a significant increase in knee flexor thickness (p<0.05). Chest and leg press strength, lean tissue mass, and muscle thickness significantly increased, while percent fat and total body mass decreased with training (p<0.05), with no difference between ALA and placebo. Conclusions: ALA lowers IL-6 in older men, but has minimal effect on muscle mass and strength during resistance training.<p>General Conclusion: A composite score of metabolic syndrome is attenuated in males supplementing with SDG. ALA reduces IL-6 in older men. Older men, but not older women, derive specific health benefits from increased consumption of components of flaxseed consumed during an exercise program.

Das Equine metabolische Syndrom, das Equine Cushing Syndrom und die häufig daraus resultierende Hufrehe stellen den behandelnden Tierarzt noch immer vor Probleme bezüglich Diagnostik und Therapie. Grund hierfür sind fehlende einheitliche endokrinologische Parameter, die eine Einschätzung des Krankheitszustandes des jeweiligen Tieres ermöglichen. Für Ponys fehlt es gänzlich an statistisch validen Referenzbereichen für die, an den Krankheiten beteiligten Hormonen. In der vorliegenden Arbeit wurde die Aktivität von Insulin, sowie die Konzentration von Insulinwachstumsfaktor-1 (IGF-1) und adrenocorticotropem Hormon (ACTH) im Blut von 130 klinisch gesunden, erwachsenen Ponys bestimmt. Damit liegen erstmals Ergebnisse vor, welche auf einer für die Erstellung von Referenzwerten ausreichend großen Fallzahl basieren. Die Analyse fand mittels eines immunometrischen Chemielumineszenz-Assays an drei aufeinander folgenden Tagen statt. Anhand einer Dreifachuntersuchung am ersten Untersuchungstag wurde für jedes Hormon der 95 %-Referenzbereich bestimmt. Für Insulin konnte ein Referenzbereich von 2,0 - 34,3 µU/ml ermittelt werden. Damit liegen die Werte unterhalb den für Großpferde veröffentlichen Werten, wobei ein direkter Vergleich nur bedingt möglich ist. Für Insulinwachstumsfaktor-1 wurden für Pferde noch keine Werte erhoben. Somit ist ein Vergleich zwischen Großpferden und Ponys diesbezüglich noch nicht möglich. Für Ponys liegt der hier ermittelte Referenzbereich zwischen 48,3 und 382,6 ng/ml. Für die Konzentration von adrenocorticotropem Hormon gibt es in der Literatur unterschiedliche Angaben sowohl für Ponys als auch für Großpferde. Mit dieser Studie wurde der 95 %-Referenzbereich für Ponys bei 6,5 bis 23,3 pg/ml ermittelt. Es konnte ein Zusammenhang zwischen dem Alter der Tiere und der ACTH-Konzentration nachgewiesen werden. Der Referenzbereich der Gruppe B (13 bis 32 Jahre) reicht von 7,1 pg/ml bis 27,7 pg/ml und unterscheidet sich damit signifikant von dem Referenzbereich der Gruppe A (drei bis 12 Jahre), welcher zwischen 5,9 pg/ml und 22,2 pg/ml ermittelt wurde. Durch die Bestimmung der Hormonkonzentration an drei aufeinander folgenden Tagen konnte die Empfindlichkeit der Hormone gegenüber enzymatischem Abbau überprüft werden. Die Proben wurden an Tag 1 aufgetaut und anschließend bei 4°C gelagert. Lediglich für adrenocorticotropes Hormon konnte eine signifikante Reduzierung (p< 0,001) der Werte um 5,4 % an Tag 3 im Vergleich zu Tag 1 festgestellt werden. Das Chemielumineszens-Assay-Testverfahren mit den Geräten der IMMULITE 2000-Reihe wurde hinsichtlich seiner Präzisionen überprüft, indem der Variationskoeffizient für die Intra-Assay-Untersuchung und die Inter-Assay-Untersuchung berechnet wurde. Für das Verfahren konnte eine ausreichende (Variationskoeffizienten ACTH: 5,2 % bzw. 5,4%), für die Untersuchung von Insulin und IGF-1 sogar eine hervorragende (Variationskoeffizienten Insulin: 3,9 % bzw. 4,7 %; Variationskoeffizienten IGF-1: 2,6 % bzw.2,9 %) Testgenauigkeit nachgewiesen werden.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 117-132).

Ο λιπώδης ιστός δεν θεωρείται πλέον αποκλειστικά παθητικός αποταμιευτικός ιστός, αλλά εκκρίνει ποικίλα βιοδραστικά πεπτίδια, γνωστά ως λιποκίνες. Η εμπλοκή των τελευταίων στην παθογένεια του μεταβολικού συνδρόμου και των επιπλοκών του τις καθιστά μόρια-στόχους που δύνανται να συμβάλουν στη θεραπευτική προσέγγιση του μεταβολικού συνδρόμου. / Adipose tissue is no more considered a passive tissue with storage function, but it has proved to be a source of a variety of bioactive peptides, described as adipokines. The implication of adipokines in the pathogenesis of metabolic syndrome and its consequences renders many of them putative target molecules in a new therapeutic approach of this syndrome.

The endocannabinoid system is a novel pharmacological target in the treatment of metabolic syndrome. Antagonism of the endocannabinoid-1 receptor (CB1R) leads to a transient reduction in food intake, a sustained decrease in body weight and an improvement in metabolic parameters in animal models of obesity. Skeletal muscle is the primary tissue involved in glucose uptake in response to insulin, and insulin sensitivity of skeletal muscle is vital to the maintenance of whole-body euglycemia. Little is known regarding the effects of CB1R antagonism on skeletal muscle glucose transport activity. The purpose of this dissertation was to test the hypothesis that antagonism of the CB1R activates signaling molecules of the insulin signaling pathway to increase glucose transport activity in normal and insulin-resistant skeletal muscle, thereby improving whole-body glucose tolerance. CB1R antagonism with SR141716 directly enhanced basal and insulin-stimulated glucose transport activity in skeletal muscle from lean and obese Zucker while activation of the CB1R with ACEA, decreased glucose transport activity. Key proteins associated with regulation of glucose transport activity were not altered by either CB1R agonism (ACEA) or antagonism (SR141716). Chronic CB1R antagonist treatment (10 mg/kg SR141716 i.p. / 14 days) also enhanced insulin-stimulated glucose transport activity in skeletal muscle of both lean and obese animals, again with no alteration in relevant signaling factors. Plasma free fatty acids (FFAs) were decreased in chronically-treated lean and obese animals and whole-body insulin sensitivity was improved in obese Zucker rats. The enhanced insulin sensitivity seen in chronically-treated obese animals was associated with a dramatic reduction in insulin secretion following a glucose challenge. Acute CB1R antagonism in obese animals also elicited a reduction in insulin secretion following a glucose challenge; however, with no improvement of whole-body insulin sensitivity. Acute CB1R antagonist treatment did not alter skeletal muscle glucose transport activity or circulating FFAs for any animals. These data suggest that although CB1R antagonism directly enhances basal and insulin stimulated glucose transport in skeletal muscle of lean and obese rats, direct action on the skeletal muscle is not responsible for the improvement in insulin-stimulated glucose transport activity and whole-body insulin sensitivity seen in chronically-treated obese animals.

The purpose of this research was to evaluate the impact of glycemic measures, and changes in identified risk factors (BMI, waist circumference, lipids, blood pressure) on follow-up glycemia, in Pima children at high risk for type two diabetes (type 2 DM).I computed incidence and cumulative incidence of type 2 DM in Pima children 5-19 years of age between 1983 and 2004. Cox proportional hazards rates for development of type 2 DM were calculated by glycemic measure (HbA1C, 20PG, FPG) controlling for confounding factors (age, sex, BMI, blood pressure, and cholesterol). Diabetes was defined by the presence of at least one of four criteria: 1) 20PG of >200 mg/dl, 2) FPG of >126 mg/dl, 3) HbA1C > 8.0%, or 4) hypoglycemic treatment. Linear regression models were computed to identify the impact of changes in risk factors on changes in HbA1C. Only exams performed in non-diabetic children during childhood were included in the regression models.Among 2658 non-diabetic children, 258 cases of diabetes occurred during mean 9.1 years of follow-up (1.5 - 21.7). The age-sex adjusted incident rate of diabetes was 19.0 cases per 1000 person-years, and cumulative incidence was 54% by age 40. Incidence rates increased with increasing baseline values of 20PG, and FPG, but not for HbA1C. For HbA1C the relationship was u-shaped with the lowest and highest quartiles having the highest DM rates. After adjustment for confounding risk factors using Cox proportional hazards analysis, the risk for diabetes increased 2-fold for every 10 mg/dl increase in FPG. Changes in waist circumference best predicted changes in HbA1C (R2 = 0.48, Ï <0.001). However, the ability of waist circumference to predict change is limited due to the powerful effect of regression to the mean, suggesting that these risk factors contribute very little to changes in HbA1C, at least in childhood.Childhood levels of glycemia predict development of type 2 DM later in life. While changes in waist circumference are associated with only moderate changes in HbA1C, this does not refute the significant contribution of adiposity in childhood to the development of type 2 DM.