Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2005.

Background: The role of dietary calcium in weight management is gaining support in the nutrition research community. It has been hypothesized that high calcium diets protect against fat gain by creating a balance of lipolysis over lipogenesis in adipocytes (Zemel et al., 2000) and that a diet deficient in calcium is associated with higher body weight and that augmenting calcium intake may reduce weight and fat gain or enhance fat loss (Shapses et al., 2004). Objectives: A lack of baseline data on the physical, physiological and mental effects of obesity on urban African women was the motivation for the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. The aim of the study was to assess the effects of obesity on health determinants of urban African and white women by comparing the lifestyle and risk factors for non-communicable diseases (NCDs) of lean, overweight and obese subjects. This led to a multi-disciplinary cross-sectional case-control study in which health determinants and health status, as well as the underlying mechanistic relationships between these factors were measured in a sample of African women volunteers. The study was repeated a year later, done in a sample of white women volunteers, POWIRS II. The effect of calcium intake on body composition was assessed during this study. Methods: One hundred and two apparently healthy urban African women, between the ages of 20 and 50 years participated in the first phase of this case-control cross-sectional survey. For a period of about three weeks, each afternoon ten subjects were to report at a Metabolic Unit Facility (consisting of 10 single bedrooms, 2 bathrooms, a living room and kitchen). Each subject received a "participant sheet" which guided them through the different research 'stations' where the various measurements were done. During the course of the evening demographic questionnaires were filled in and all anthropometric measurements were taken, except weight and height measurements. All participants received an identical light supper which excluded alcohol and caffeine at 20h00, went to sleep before 23h00 and fasted overnight. From 06h00 in the morning weight, height and blood pressure measurements were taken. After a fasting blood sample was taken, a two-hour glucose tolerance test commenced. Subjects received a breakfast and afterwards habitual dietary intake questionnaires were completed. Results: Mean total dietary calcium intake as significantly higher in white women (POWIRS II), with a mean intake 1053.8 mg per day, as opposed to a mean intake of 494.8 mg calcium per day in the blacks subjects (POWIRS I). Mean fat intake in the black subjects was 59.3 g per day, and in the white women 103.1 g per day. Thus the calcium:fat ratio in white women was higher than in black women (11.0 and 8.4 respectively). After adjustment for age and total dietary energy intake, significant negative correlations were found between dietary calcium intake and various variables, only in the white subjects. These were BMI (r=-0.255, p=0.01), percentage body fat (r=-0.252, p=0.01), fasting insulin (r=-0.205, p=0.05) and fasting glucose (r=-0.199, p=0.046). The calcium:fat ratio correlated negatively with BMI (r=-0.378, p<0.0001), percentage body fat (r=-0.401, p<0.0001), fasting glucose (r=-0.229, p=0.02), fasting insulin (r=-0.212, p=0.04) and plasma leptin (r=-0.284, p=0.004). Adjustment for smoking resulted in slightly different correlation coefficients, but similar significant correlations were still found. The only significant association that was found in the black population, was a negative correlation between dietary calcium intake and systolic blood pressure (p=0.03) as well as diastolic blood pressure (p=0.04). After adjustment for age, smoking and dietary energy intake no significant correlations were found in the black subjects. Conclusion: The results from the POWIRS study in white women are consistent with the hypothesis that there may be an inverse relationship between adiposity and calcium intake. In our study higher calcium intakes were associated with lower body fat, lower BMI, lower fasting glucose and insulin, as well as plasma leptin in white women. The association seems to be significant in subjects with high intakes of fat and calcium (as seen in the white women). / Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2005.

Background: The role of dietary calcium in weight management is gaining support in the nutrition research community. It has been hypothesized that high calcium diets protect against fat gain by creating a balance of lipolysis over lipogenesis in adipocytes (Zemel et al., 2000) and that a diet deficient in calcium is associated with higher body weight and that augmenting calcium intake may reduce weight and fat gain or enhance fat loss (Shapses et al., 2004). Objectives: A lack of baseline data on the physical, physiological and mental effects of obesity on urban African women was the motivation for the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. The aim of the study was to assess the effects of obesity on health determinants of urban African and white women by comparing the lifestyle and risk factors for non-communicable diseases (NCDs) of lean, overweight and obese subjects. This led to a multi-disciplinary cross-sectional case-control study in which health determinants and health status, as well as the underlying mechanistic relationships between these factors were measured in a sample of African women volunteers. The study was repeated a year later, done in a sample of white women volunteers, POWIRS II. The effect of calcium intake on body composition was assessed during this study. Methods: One hundred and two apparently healthy urban African women, between the ages of 20 and 50 years participated in the first phase of this case-control cross-sectional survey. For a period of about three weeks, each afternoon ten subjects were to report at a Metabolic Unit Facility (consisting of 10 single bedrooms, 2 bathrooms, a living room and kitchen). Each subject received a "participant sheet" which guided them through the different research 'stations' where the various measurements were done. During the course of the evening demographic questionnaires were filled in and all anthropometric measurements were taken, except weight and height measurements. All participants received an identical light supper which excluded alcohol and caffeine at 20h00, went to sleep before 23h00 and fasted overnight. From 06h00 in the morning weight, height and blood pressure measurements were taken. After a fasting blood sample was taken, a two-hour glucose tolerance test commenced. Subjects received a breakfast and afterwards habitual dietary intake questionnaires were completed. Results: Mean total dietary calcium intake as significantly higher in white women (POWIRS II), with a mean intake 1053.8 mg per day, as opposed to a mean intake of 494.8 mg calcium per day in the blacks subjects (POWIRS I). Mean fat intake in the black subjects was 59.3 g per day, and in the white women 103.1 g per day. Thus the calcium:fat ratio in white women was higher than in black women (11.0 and 8.4 respectively). After adjustment for age and total dietary energy intake, significant negative correlations were found between dietary calcium intake and various variables, only in the white subjects. These were BMI (r=-0.255, p=0.01), percentage body fat (r=-0.252, p=0.01), fasting insulin (r=-0.205, p=0.05) and fasting glucose (r=-0.199, p=0.046). The calcium:fat ratio correlated negatively with BMI (r=-0.378, p<0.0001), percentage body fat (r=-0.401, p<0.0001), fasting glucose (r=-0.229, p=0.02), fasting insulin (r=-0.212, p=0.04) and plasma leptin (r=-0.284, p=0.004). Adjustment for smoking resulted in slightly different correlation coefficients, but similar significant correlations were still found. The only significant association that was found in the black population, was a negative correlation between dietary calcium intake and systolic blood pressure (p=0.03) as well as diastolic blood pressure (p=0.04). After adjustment for age, smoking and dietary energy intake no significant correlations were found in the black subjects. Conclusion: The results from the POWIRS study in white women are consistent with the hypothesis that there may be an inverse relationship between adiposity and calcium intake. In our study higher calcium intakes were associated with lower body fat, lower BMI, lower fasting glucose and insulin, as well as plasma leptin in white women. The association seems to be significant in subjects with high intakes of fat and calcium (as seen in the white women). / Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2005.

abstract: The winter holiday period has been highlighted as a major risk period for weight gain due to excess caloric intake in the form of fat and sugar. Furthermore, diets high in fat and sugar have been implicated in the pathogenesis of diabetes and cardiovascular disease. Exercise aids in the prevention of weight/fat gain, and prevents deleterious changes in cardiometabolic function. The objective of this study was to examine the effects of a fat-sugar supplemented diet, with and without two different exercise training protocols, on body composition, glycemic control and other markers of cardiovascular disease in an at-risk population of overweight and obese males. Twenty-seven, healthy overweight/obese (BMI >25 kg/m2) males were fed 2 donuts per day, 6 days/week, for four weeks, while maintaining their current diet. In addition, all subjects were randomized to one of the following conditions: sedentary control, 1,000 kcal/week moderate-intensity continuous training (MICT) (50% of peak oxygen consumption), or 1,000 kcal/week high-intensity interval training (HIIT) (90-95% of peak heart rate). Supervised exercise training was performed 4 days/week on a cycle ergometer. Changes in body weight and composition, endothelial function, arterial stiffness, glycemic control, blood lipids and cardiorespiratory fitness (CRF) were assessed before and after the intervention. Body weight, lean mass and visceral fat increased significantly in HIIT (p<0.05) and were unchanged in MICT. There was a trend for a significant increase in body weight (p=0.07) and lean mass (p=0.11) in control. Glycemic control during the 2-h OGTT improved significantly in MICT and control, with no change in HIIT. Hepatic insulin resistance index (IRI) and 30-min insulin during the OGTT improved significantly after MICT and worsened following control (p=0.03), while HIIT was unchanged. CRF increased significantly in both HIIT and MICT, with no change in control (p<0.001). There were no significant changes in other markers of cardiovascular disease. The addition of a fat-sugar supplement (~14,500 kcal) over a 4-week period was not sufficient to induce deleterious changes in body composition and cardiometabolic health in overweight/obese young males. Exercise training did not afford overweight/obese males additional health benefits, with the exception of improvements in fitness and hepatic IRI. / Dissertation/Thesis / Doctoral Dissertation Physical Activity, Nutrition and Wellness 2016

No description available.

<p>Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of ageing, but its measurement <i>in vivo</i> has been difficult. The aim of this thesis was to evaluate methods for measurement of lipid peroxidation <i>in vivo</i> that are suitable for clinical investigations, and to apply these methods in animal and human studies investigating basal conditions and situations associated with increased lipid peroxidation.</p><p>The ferrous oxidation in xylenol orange assay for quantification of total plasma lipid hydroperoxides was re-evaluated regarding sample handling and storage. It was shown to be a useful tool for analyses of fresh but not stored plasma samples.</p><p>A methodology for measurement of the total amount (sum of free and esterified) of an F₂-isoprostane, 8-iso-prostaglandin F_2α, in tissues using alkaline hydrolysis in combination with an existing radioimmunoassay was developed. High levels of 8-iso-prostaglandin F_2α in rat liver tissue were quantified by this technique both at basal conditions and in an experimental model of increased lipid peroxidation induced by carbon tetrachloride.</p><p>Supplementation with vitamin E to rats decreased both non-enzymatic and enzymatic lipid peroxidation as measured by 8-iso-prostaglandin F_2α and a major prostaglandin F_2α metabolite. This was verified both in the urine at basal conditions, and in the urine and liver tissue after carbon tetrachloride induced lipid peroxidation.</p><p>In a randomised cross-over study in humans, a rapeseed oil-based diet with an increased proportion of easily oxidised polyunsaturated fatty acids was compared to a control diet rich in saturated fats. The rapeseed oil-based diet did not seem to increase the degree of lipid peroxidation in plasma and urine as measured by 8-iso-prostaglandin F_2α, hydroperoxides and malondialdehyde, presumably due to a sufficient content of antioxidants in the rapeseed oil diet.</p><p>In conclusion, the simultaneous measurement of several biomarkers of lipid peroxidation is a promising approach for future studies investigating the possible role of lipid peroxidation <i>in vivo</i> under basal conditions and in the pathology of diseases.</p>

<p>Insulin sensitivity is related to the fatty acid profile of skeletal muscle. The aim of this thesis was to investigate whether physical activity and dietary fat quality, independent of each other, influence the fatty acid composition of the skeletal muscle lipids. In an intervention study where middle-aged men were exercising for six weeks, and in a cross-sectional study comparing sedentary with endurance trained young men, it was demonstrated that the fatty acid composition of skeletal muscle lipids differed between physical active and inactive men. In brief, a lower proportion of palmitic acid (16:0) and total n-6 polyunsaturated fatty acids (PUFA) and a higher proportion of stearic (18:0) and oleic acid (18:1n-9) and total n-3 PUFA in the muscle phospholipids were associated with physical activity, despite similar fatty acid composition of the diet. In the second study, that included a larger training volume, differences in the fatty acid profile were also found in the skeletal muscle triglycerides. </p><p>In contrast, after short-term supra-maximal exercise we found no significant changes in the proportion of the fatty acids in skeletal muscle. </p><p>Furthermore, after a treatment period of three months, with diets with various dietary fat quality, the proportions of saturated fatty acids (14:0, 15:0 and 17:0) were higher and the proportion of 18:1 n-9 lower in subjects with a high intake of saturated fatty acids compared with subjects with a high intake of monounsaturated fatty acids. In addition subjects given n-3 supplementation had a higher proportion of total n-3 PUFA and lower n-6 PUFA in the skeletal muscle phospholipids than controls. Differences similar to those observed in the phospholipids were found in the triglycerides. </p><p>In summary, these results suggest that regular aerobic physical activity and dietary fat quality influence the fatty acid composition of the skeletal muscle lipids, which may affect insulin sensitivity and glucose homeostasis. </p>

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of ageing, but its measurement in vivo has been difficult. The aim of this thesis was to evaluate methods for measurement of lipid peroxidation in vivo that are suitable for clinical investigations, and to apply these methods in animal and human studies investigating basal conditions and situations associated with increased lipid peroxidation. The ferrous oxidation in xylenol orange assay for quantification of total plasma lipid hydroperoxides was re-evaluated regarding sample handling and storage. It was shown to be a useful tool for analyses of fresh but not stored plasma samples. A methodology for measurement of the total amount (sum of free and esterified) of an F2-isoprostane, 8-iso-prostaglandin F2α, in tissues using alkaline hydrolysis in combination with an existing radioimmunoassay was developed. High levels of 8-iso-prostaglandin F2α in rat liver tissue were quantified by this technique both at basal conditions and in an experimental model of increased lipid peroxidation induced by carbon tetrachloride. Supplementation with vitamin E to rats decreased both non-enzymatic and enzymatic lipid peroxidation as measured by 8-iso-prostaglandin F2α and a major prostaglandin F2α metabolite. This was verified both in the urine at basal conditions, and in the urine and liver tissue after carbon tetrachloride induced lipid peroxidation. In a randomised cross-over study in humans, a rapeseed oil-based diet with an increased proportion of easily oxidised polyunsaturated fatty acids was compared to a control diet rich in saturated fats. The rapeseed oil-based diet did not seem to increase the degree of lipid peroxidation in plasma and urine as measured by 8-iso-prostaglandin F2α, hydroperoxides and malondialdehyde, presumably due to a sufficient content of antioxidants in the rapeseed oil diet. In conclusion, the simultaneous measurement of several biomarkers of lipid peroxidation is a promising approach for future studies investigating the possible role of lipid peroxidation in vivo under basal conditions and in the pathology of diseases.

Insulin sensitivity is related to the fatty acid profile of skeletal muscle. The aim of this thesis was to investigate whether physical activity and dietary fat quality, independent of each other, influence the fatty acid composition of the skeletal muscle lipids. In an intervention study where middle-aged men were exercising for six weeks, and in a cross-sectional study comparing sedentary with endurance trained young men, it was demonstrated that the fatty acid composition of skeletal muscle lipids differed between physical active and inactive men. In brief, a lower proportion of palmitic acid (16:0) and total n-6 polyunsaturated fatty acids (PUFA) and a higher proportion of stearic (18:0) and oleic acid (18:1n-9) and total n-3 PUFA in the muscle phospholipids were associated with physical activity, despite similar fatty acid composition of the diet. In the second study, that included a larger training volume, differences in the fatty acid profile were also found in the skeletal muscle triglycerides. In contrast, after short-term supra-maximal exercise we found no significant changes in the proportion of the fatty acids in skeletal muscle. Furthermore, after a treatment period of three months, with diets with various dietary fat quality, the proportions of saturated fatty acids (14:0, 15:0 and 17:0) were higher and the proportion of 18:1 n-9 lower in subjects with a high intake of saturated fatty acids compared with subjects with a high intake of monounsaturated fatty acids. In addition subjects given n-3 supplementation had a higher proportion of total n-3 PUFA and lower n-6 PUFA in the skeletal muscle phospholipids than controls. Differences similar to those observed in the phospholipids were found in the triglycerides. In summary, these results suggest that regular aerobic physical activity and dietary fat quality influence the fatty acid composition of the skeletal muscle lipids, which may affect insulin sensitivity and glucose homeostasis.

ABSTRACTThe prevalence of diabetes is increasing dramatically, incurring a major health and socioeconomic burden. Type 2 diabetes (T2D), the most prevalent form of diabetes, results from a variable combination of insulin resistance and insulin deficiency, secondary to pancreatic β-cell failure. These defects are caused by a complex interplay between genetic and environmental/ lifestyle factors. Among the latter, poor dietary quality is a crucial driver of T2D development. Although adopting healthy dietary habits is considered as a mainstay for T2D prevention, what constitutes a healthy diet remains controversial. Epidemiological studies examining the association of dietary fat quality with T2D incidence have yielded equivocal results and may suffer from confounding. On the other hand, randomized trials assessing the impact of dietary fat saturation on glucose homeostasis have major methodological shortcomings, precluding reliable conclusions. In order to elucidate this question, we compared the effects of palm oil vs olive oil on glucose homeostasis and other relevant metabolic parameters, in a mouse model of high-fat diet-induced obesity. The saturated fatty acid-rich palm oil is the most abundantly used oil worldwide. Olive oil is a staple food of the Mediterranean diet, rich in monounsaturated fatty acids and widely regarded as healthful. In this model, palm oil was not more harmful than olive oil with regard to glucose/insulin homeostasis. However, palm oil was associated with increased visceral adiposity and triglyceridemia compared to olive oil. Circulating and tissue free fatty acid (FFA) concentration and composition are determined by dietary factors, as well as genetic and metabolic factors. There is accumulating evidence indicating that increased FFA levels and/or an unbalanced FFA composition with excess palmitate, induce β-cell dysfunction and apoptosis (lipotoxicity). To characterize the mechanisms underlying lipotoxicity, we combined RNA-sequencing with proteomics of β-cells exposed to palmitate, the most prevalent SFA in humans. This cross-omics study showed that palmitate altered lipid and amino-acid metabolism, and affected amplifying pathways of insulin secretion and exocytosis. Furthermore, palmitate induced stress pathways, including mitochondrial dysfunction, oxidative stress and endoplasmic reticulum (ER) stress. ER stress is triggered when protein folding demand exceeds ER folding capacity. This response aims to restore ER homeostasis but if unresolved, it can become deleterious. Islets from T2D patients display signs of ER stress, pointing to a potentially pathogenic role of the latter.Monogenic and neonatal diabetes are rare forms of diabetes caused by single gene mutations. These forms are of particular interest, as they can serve as ‘human knockout’ models of diabetes. Recent evidence shows that there is overlap in the genetic basis of monogenic diabetes and T2D, suggesting that they may be part of a pathologic continuum. To explore the role of ER stress in diabetes pathogenesis, we studied two different genetic syndromes involving neonatal or early-onset diabetes, caused by mutations in genes related to ER function (DNAJC3 and YIPF5). Using in vitro knockdown models, we showed that ER stress elicited by impaired chaperone function (DNAJC3) or by impaired ER-to-Golgi protein transport (YIFP5) causes β-cell apoptosis. Altogether, our findings support that lipotoxic and genetic ER stress contribute to diabetes pathogenesis. Preventing or modulating ER stress thus holds anti-diabetic therapeutic potential. Future research should focus on defining optimal strategies to restore a balanced FFA profile and enhance ER function, aiming to prevent ER-stress induced β-cell failure. RésuméLa prévalence du diabète progresse constamment, posant un défi sanitaire et socioéconomique majeur. Le diabète de type 2 (DT2), la forme la plus courante de diabète, résulte de la résistance à l’insuline, en association avec un déficit insulinique dû à la défaillance des cellules β pancréatiques. Ces anomalies découlent d’une interaction complexe entre des facteurs génétiques et des facteurs liés au mode de vie. Parmi ces derniers, la qualité du régime alimentaire est un facteur crucial pour le développement du DT2. Bien que le suivi d’un régime alimentaire sain est considéré comme le pilier pour la prévention du DT2, ce qui constitue un régime sain demeure un sujet de controverse.Les études épidémiologiques examinant l’association entre la qualité de la graisse alimentaire et l’incidence du DT2 ont donné des résultats équivoques, affectés éventuellement par des facteurs confondants. En outre, les études randomisées évaluant l’impact du degré de saturation de la graisse alimentaire sur l’homéostasie du glucose comportent des limitations méthodologiques majeures. Afin d’élucider cette question, on a comparé les effets de l’huile de palme aux effets de l’huile d’olive sur l’homéostasie du glucose et d’autres paramètres métaboliques pertinents. Dans ce but, on a utilisé un modèle murin d’obésité induite par un régime riche en graisse. L’huile de palme est riche en acides gras saturés et elle est l’huile la plus utilisée globalement. L’huile d’olive est un aliment phare du régime Méditerranéen, riche en acides gras monoinsaturés et généralement reconnu comme un aliment sain. Dans notre modèle murin, la consommation d’huile de palme n’était pas plus néfaste que celle de l’huile d’olive sur l’homéostasie du glucose, la sensibilité à l’insuline et l’insulinosécrétion. Par contre, l’huile de palme était associée à une adiposité viscérale et une triglycéridémie plus élevée comparée à l’huile d’olive.La concentration et la composition des acides gras libres (AGL) sont déterminées par des facteurs alimentaires, génétiques et métaboliques. Des données abondantes démontrent que la présence des niveaux élevés d’AGL et/ou d’une composition déséquilibrée d’AGL induit la dysfonction et l’apoptose des cellules β (lipotoxicité). Pour caractériser les mécanismes sous-jacents de la lipotoxicité, on a combiné un séquençage ARN à une étude protéomique des cellules β exposées au palmitate, l’AGL saturé le plus courant chez l’homme. Cette étude conjointe a montré que le palmitate altère le métabolisme des lipides et des acides aminés, les voies d’amplification de la sécrétion d’insuline et l’exocytose. Le palmitate induit également des voies de stress cellulaires, telles que la dysfonction mitochondriale, le stress oxydatif et le stress du réticulum endoplasmique (RE). Le stress du RE est activé quand les besoins en sécrétion protéique dépassent les capacités de l’organite. Cette réponse a pour but de rétablir l’homéostasie du RE mais si le stress reste non résolu, ceci peut s’avérer délétère. Des îlots des patients avec un DT2 montrent des signes de stress du RE, évoquant un rôle potentiellement pathogénique de ce dernier.Le diabète monogénique et néonatal sont des formes rares de diabète causées par des mutations d’un seul gène. Ces formes sont particulièrement intéressantes sur le plan physiopathologique car elles représentent des ‘knockout’ humains. Des données récentes montrent que la base génétique du diabète monogénique n’est pas complètement distincte de celle du diabète de type 2 et les deux entités pourraient faire partie d’un continuum. Afin d’explorer le rôle du stress du RE dans la pathogénèse du diabète, on a étudié deux syndromes génétiques entraînant un diabète néonatal ou à début très précoce. Ces syndromes sont causés par des mutations dans des gènes impliqués dans la fonction du RE (DNAJC3 et YIPF5). En silençant ces gènes in vitro, on a montré que le stress du RE, déclenché soit par une dysfonction des chaperones (DNAJC3), soit par un retard du trafic de protéines du RE vers le Golgi (YIPF5), induit l’apoptose des cellules β.Ces résultats suggèrent que le stress du RE génétique et lipotoxique contribuent à la pathogénèse du diabète. La prévention ou modulation du stress du RE présente donc un potentiel thérapeutique anti-diabétique. Des études futures pourraient permettre de définir des stratégies optimales pour rétablir un profil d’AGL équilibré ou renforcer la fonction du RE, en vue de prévenir la défaillance des cellules β. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished