[Truncated abstract] Obesity is now a major public health problem worldwide. More than half the Australian population is now overweight. This is an important public health concern primarily because of the impact of overweight and obesity on risk of diabetes, hypertension and cardiovascular disease. Many strategies have been proposed to fight the obesity epidemic. One possible strategy involves understanding of the role of dietary components in the control of food intake. In this regard, dietary protein and fibre appear to be the most satiating nutrients. Foods enriched in protein, replacing energy from carbohydrate, or dietary fibre can increase satiety and reduce energy intake in the short-term. Longer-term trials suggest benefits of increasing protein or fibre intake on weight loss and features of the metabolic syndrome. The effects of dietary approaches which increase both protein and fibre at the expense of refined carbohydrate are uncertain. A practical approach to increasing both protein and fibre content of processed foods is to incorporate high protein and fibre ingredients into high carbohydrate foods. Lupin kernel flour is a novel food ingredient derived from the endosperm of lupin. It contains 40 to 45% protein, 25 to 30% fibre, and negligible sugar and starch. Lupin kernel flour can be incorporated into refined carbohydrate rich foods such as bread to increase protein and fibre content at the expense of refined carbohydrate. ... Body weight was measured every 2 weeks throughout the 16 week intervention, and these data were analysed to determine whether there was any between group difference in the rate of change in weight over 16 weeks. Over 16 weeks, lupin bread compared to white bread resulted in a significant increase in protein (13.7 (2.3, 25.0) g/d) and fibre (12.5 (8.8, 16.2) g/d) intakes, and a decrease in carbohydrate intake (-19.9 (-45.2, 5.5) g/d). There was a significant difference between groups in the rate of weight change over the 16 weeks (P=0.05). However, at 16 weeks there was no significant effect on body weight (-0.4 (-1.3, 0.6) kg), fat mass (-0.5 (-1.2, 0.2) kg) or fat free mass (0.2 (-0.5, 0.8) kg). Plasma adiponectin and leptin were not altered. Mean 24 hour systolic blood pressure (-2.4 (-3.4, -1.3) mm Hg) and pulse pressure (-3.1 (-3.9, -2.3) mm Hg) were lower for lupin relative to white bread, but diastolic blood pressure was not significantly different between groups. Apart from a lower HDL cholesterol for lupin relative to white bread (-0.09 (-0.17, -0.01) mmol/L), there were no significant differences in other blood lipids and glucose and insulin concentrations. Interpretation of the results was not influenced after adjustment for potential confounding factors. These studies assessed effects of bread enriched in lupin kernel flour relative to white bread, resulting in a higher protein and fibre intake and lower refined carbohydrate intake. This increased satiety and reduced energy intake acutely, but did not significantly influence body weight over 16 weeks. Systolic blood pressure and pulse pressure were significantly reduced. There were no significant improvements in blood lipids or glucose and insulin concentrations. Therefore, increasing protein and fibre intake at the expense of refined carbohydrate using lupin kernel flour may benefit satiety and blood pressure. Longer-term trials incorporating weight loss may be needed to observe benefits on body weight.

The objective of this thesis was to determine the association of leg length (LL), a marker of early childhood conditions, with metabolic abnormalities underlying type 2 diabetes. Utilizing data from a population at-risk for diabetes, the associations of LL with i) insulin resistance (IR) and beta-cell dysfunction and ii) a continuous metabolic syndrome risk score (MetScore) were analyzed. Results showed that shorter LL was associated with IR and beta-cell dysfunction, and that the combination of short legs and large waist (a marker of adult obesogenic conditions) was associated with the greatest IR. Height, a marker of overall childhood conditions, was found to be inversely associated with the MetScore. Therefore, both adverse childhood conditions and early-late life mismatched conditions may increase the risk for diabetes through differing pathways. Improving childhood conditions (i.e. nutritionally or economically) may be an important strategy to prevent diabetes.

The objective of this thesis was to determine the association of leg length (LL), a marker of early childhood conditions, with metabolic abnormalities underlying type 2 diabetes. Utilizing data from a population at-risk for diabetes, the associations of LL with i) insulin resistance (IR) and beta-cell dysfunction and ii) a continuous metabolic syndrome risk score (MetScore) were analyzed. Results showed that shorter LL was associated with IR and beta-cell dysfunction, and that the combination of short legs and large waist (a marker of adult obesogenic conditions) was associated with the greatest IR. Height, a marker of overall childhood conditions, was found to be inversely associated with the MetScore. Therefore, both adverse childhood conditions and early-late life mismatched conditions may increase the risk for diabetes through differing pathways. Improving childhood conditions (i.e. nutritionally or economically) may be an important strategy to prevent diabetes.

[Truncated abstract] Arachidonic acid is oxidised in vivo by non-enzymatic (free radical) or enzymatic pathways (cyclooxygenase, lipoxygenase, and cytochrome P450) to form a range of biologically active eicosanoids. Specifically, arachidonic acid is metabolised by cytochrome P450 -hydroxylase to produce vasoactive 20-hydroxyeicosatetraenoic acid (20-HETE), and by 5-lipoxygenase to produce proinflammatory leukotriene B4 (LTB4), which can further be metabolised by -hydroxylase to from 20-OH-LTB4 and 20-COOH-LTB4. F2-Isoprostanes (F2-IsoPs) are produced through free radical attack on arachidonic acid and have been recognised as the most reliable markers of lipid peroxidation in vivo. The metabolic syndrome (MetS) is characterised by abdominal obesity, hypertension, insulin resistance, glucose intolerance, and dyslipidemia. It is associated with low-grade inflammation and oxidative stress and an increased risk of developing cardiovascular diseases. Dietary weight loss is strongly recommended for the management of the MetS and can potentially minimise the risk of cardiovascular diseases and diabetes in individuals with the MetS. Little is known regarding the role of these arachidonic acid metabolites in the MetS and the effect of weight loss on their metabolism. Chapter three comprised of three in vitro studies aimed to examine 20-HETE synthesis in human blood cells. 20-HETE acts as a second messenger for vasoconstrictor actions of angiotensin II (Ang II) and endothelin-1 (ET-1) in renal and mesenteric beds. Human neutrophils and platelets are integral to the inflammatory process. ... Production of LTB4 and 20-OH-LTB4 was significantly lower compared with controls (P<0.005) and remained so after adjustment for neutrophil count (P<0.05).The weight loss intervention resulted in a 4.6kg reduction in body weight and a 6.6cm decrease in waist circumference and a significant increase in LTB4 and 20-OH- LTB4 in the weight loss group. Chapter Five continued to investigate the role of other arachidonic acid metabolites, 20-HETE and F2-IsoPs in the MetS and the effect of weight loss. In the case-control study (Human study 1), plasma and urinary 20-HETE and F2-IsoPs were significantly elevated in the MetS group, but no significant difference was found in stimulated-neutrophil 20-HETE. A significant gender x group interaction was observed in that women with the MetS had higher urinary 20-HETE and F2-IsoPs compared to controls (P<0.0001). In a randomised controlled trial (Human study 2), relative to the weight- maintenance group, a 4.6 kg loss in weight resulted in a 2 mmHg fall in blood pressure but did not alter the production of 20-HETE or F2-IsoPs. No significant differences were shown in 20-HETE released from stimulated-neutrophils before and after weight loss. 20-HETE and oxidative stress may be important mediators of cardiovascular disease risk in the MetS. Although a 4% reduction in body weight reduced BP, there were no changes in plasma or urinary 20-HETE or F2-IsoPs. In summary, in vitro studies show that human neutrophils and platelets can produce 20-HETE in response to Ang II and ET-1, and human studies demonstrate that the presence of MetS has a significant impact on arachidonic acid metabolism and effective weight loss can restore leukocyte synthesis of LTB4.

Thesis (M. A. (Physiology)) -- University of Limpopo, 2022 / Background: Metabolic syndrome (MetS) is amongst the underlying causes of mortality and morbidity globally. However, lifestyle habits such as frequent consumption of sugar-sweetened beverages (SSBs) contributes to its onset. The study was aimed at investigating the association between MetS and SSBs intake among Ellisras rural youth. Additionally, to find the best obesity indices to predict MetS. Methods: The current study included a total of 593 Ellisras rural youth, aged 22 to 30 years (289 males and 304 females). Anthropometric measurements, blood pressure (BP), and biochemical assessment were taken using standards procedures. A validated 24hrs recall questionnaire and food manuals were used to collect SSBs data. Binary logistic regression was applied to determine the association between SSBs intake and MetS components for the adjusted model. Confirmatory factor analysis was used to test the best single-factor models to predict MetS on commonly selected obesity indices. Results: The SSBs quartile 4 was associated with a high risk of high fasting blood glucose (FBG) for adjusted (OR=2.32; CI=1.15-4.70; p<0.05) and unadjusted (OR=2.34; CI=1.16-4.73; p<0.05) models were a significant linear trend (p for trend=0.049) in males was found. Low risk of reduced high density lipoprotein cholesterol (HDL-C) was associated with the second and fourth SSBs quartiles for unadjusted ((OR=0.40; CI=0.18-0.85; p<0.05; OR=0.37; CI=0.13-0.80; p<0.05) respectively and adjusted model (OR=0.40; CI=0.18-0.85; p<0.05; OR=0.37; CI=0.17-0.80; p<0.05) respectively in females. Moreover, the fourth SSBs quartile was likely to decrease the risk of high triglycerides (TG) for unadjusted (OR=0.12; CI=0.01-0.87; p<0.05) and adjusted (OR=0.10; CI=0.01-0.83; p<0.05) models were the significant linear trend (p= trend 0.006) was observed also in females. There was a significant linear trend association between SSBs quartiles consumption and high TG in males and high waist circumference (WC) in females, but logistic regression analysis didn’t depict any significant association (p>0.05). In males, single model fit built based on WC (comparative fit index (CFI)=1.00; turker lewis index (TLI)=1.05; RMSEA=0.00; akaike information criterion (AIC)=-2680) and waist to height ratio v (WHtR) (RMSEA=0.00, CFI=1.00; AIC=-2662, TLI=1.05;) suggested a better fit index as compared to body mass index (BMI) and neck circumference (NC). Among females, a single model fit built on NC obtained a better fit index (RMSEA=0.05, CFI=0.90, and AIC= -429.21, TLI=0.71). Conclusion: In this study, there was an association between SSBs consumption and some MetS components (high TG, reduced HDL-C, and high FBG). Obesity indices including WHtR, NC, and WC were the best predictors of MetS. Future studies are recommended to further investigate the association of the risk of MetS and the consumption SSBs and the best obesity indices to predict MetS to assist in efforts to help curb MetS and related risk factors in rural areas of South Africa.

Background In South Africa, as in many other developing countries, obesity has become a major health problem causing an increase in the incidence and prevalence of various non-communicable diseases. Research has shown that excess adiposity is associated with low vitamin D status and detrimental to bone health. Low vitamin D status has been linked to various non-communicable diseases which includes osteoporosis, and also the metabolic syndrome. Information is scarce on the role of lean mass and fat mass on bone health in the black South African population. There is also a shortage of data on the association between vitamin D status and the metabolic syndrome in the South African population. Aim The main aim of this study was to examine factors (vitamin D status, socio-economic status [SES] and lifestyle risk factors) associated with body composition, including bone health, as well as predictors of change in body composition in African adults in the North West Province of South Africa. Methods The first study that forms part of this thesis was a longitudinal study aimed at examining the effects of urbanization, socio-economic status and lifestyle factors on changes in body composition over 5 years in rural and urban black South African adults. A total of 1058 men and women above age 30 years from the Prospective Urban Rural Epidemiology study were included in this study. The second study to form part of this thesis aimed to examine the association between body composition and bone health in urban black South African women. Structured questionnaires were used to collect socio-demographic and lifestyle information including medication and tobacco use. This second study is cross-sectional in design and it included 189 postmenopausal women aged > 43 years old. Dual X-ray absorptiometry was used to assess bone mineral density, lean mass and fat mass, while structured and specific questionnaires were used to assess the habitual physical activity, food frequency and fracture risk. Habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. The third study aimed to examine the association of serum 25 hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentration, respectively, with the metabolic syndrome while controlling for adiposity in black women in the North West Province, South Africa. This third study is also cross-sectional in design and it included 209 HIV-negative urban women. Dual X-ray absorptiometry was used to assess adiposity, while habitual physical activity was accessed with questionnaire and habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. Results Study 1: Over a 5-year period, body mass index (BMI) and waist circumference increased in both genders, but the change was significant for BMI (P<0.01) and waist circumference (P<0.001) in women only, indicating an increase in adiposity over time. Urban residency positively predicted changes in waist circumference in men (p < 0.05) and women (p < 0.001) as well as change in triceps skinfold thickness of men (p < 0.05). Being married positively predicted changes in BMI (p < 0.001) and waist circumference (p < 0.001) in men, while age negatively predicted changes in triceps skinfold thickness in women (p < 0.001). Study 2: Fat mass and lean mass were significantly positively associated with bone mineral density (BMD) and fracture risk when adjusted for potential confounders. However, lean mass and not fat mass remained significantly associated with femoral neck BMD (β = 0.49, p <0.001), spine BMD (β = 0.48, p< 0.0001) and hip BMD (β = 0.59, p< 0.0001). Lean mass was also negatively associated with fracture risk (β = -0.19 p =0.04) when both lean and fat mass were in the same model. Study 3: After adjusting for age, body fat, habitual physical activity, tobacco use and season, neither 25(OH)D nor PTH concentrations showed significant associations with having the metabolic syndrome. However, when body fat was replaced with waist circumference there was a weak positive association between 25(OH)D concentration and the metabolic syndrome. No significant association was found between PTH:25(OH)D ratio and the metabolic syndrome. Conclusion This thesis has highlighted that the prevalence of obesity among black South Africans is high particularly among women and urbanization played a significant role in the increasing adiposity of black South Africans in the North West province. Lean mass had a stronger association with bone health in comparison to fat mass in urban black South African women. Low 25(OH)D concentration was not associated with the metabolic syndrome while there was no significant association between PTH and the metabolic syndrome in our black South African women. / PhD (Dietetics), North-West University, Potchefstroom Campus, 2015

Background In South Africa, as in many other developing countries, obesity has become a major health problem causing an increase in the incidence and prevalence of various non-communicable diseases. Research has shown that excess adiposity is associated with low vitamin D status and detrimental to bone health. Low vitamin D status has been linked to various non-communicable diseases which includes osteoporosis, and also the metabolic syndrome. Information is scarce on the role of lean mass and fat mass on bone health in the black South African population. There is also a shortage of data on the association between vitamin D status and the metabolic syndrome in the South African population. Aim The main aim of this study was to examine factors (vitamin D status, socio-economic status [SES] and lifestyle risk factors) associated with body composition, including bone health, as well as predictors of change in body composition in African adults in the North West Province of South Africa. Methods The first study that forms part of this thesis was a longitudinal study aimed at examining the effects of urbanization, socio-economic status and lifestyle factors on changes in body composition over 5 years in rural and urban black South African adults. A total of 1058 men and women above age 30 years from the Prospective Urban Rural Epidemiology study were included in this study. The second study to form part of this thesis aimed to examine the association between body composition and bone health in urban black South African women. Structured questionnaires were used to collect socio-demographic and lifestyle information including medication and tobacco use. This second study is cross-sectional in design and it included 189 postmenopausal women aged > 43 years old. Dual X-ray absorptiometry was used to assess bone mineral density, lean mass and fat mass, while structured and specific questionnaires were used to assess the habitual physical activity, food frequency and fracture risk. Habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. The third study aimed to examine the association of serum 25 hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentration, respectively, with the metabolic syndrome while controlling for adiposity in black women in the North West Province, South Africa. This third study is also cross-sectional in design and it included 209 HIV-negative urban women. Dual X-ray absorptiometry was used to assess adiposity, while habitual physical activity was accessed with questionnaire and habitual activity energy expenditure was also measured using an accelerometer with a combined heart rate monitor. Results Study 1: Over a 5-year period, body mass index (BMI) and waist circumference increased in both genders, but the change was significant for BMI (P<0.01) and waist circumference (P<0.001) in women only, indicating an increase in adiposity over time. Urban residency positively predicted changes in waist circumference in men (p < 0.05) and women (p < 0.001) as well as change in triceps skinfold thickness of men (p < 0.05). Being married positively predicted changes in BMI (p < 0.001) and waist circumference (p < 0.001) in men, while age negatively predicted changes in triceps skinfold thickness in women (p < 0.001). Study 2: Fat mass and lean mass were significantly positively associated with bone mineral density (BMD) and fracture risk when adjusted for potential confounders. However, lean mass and not fat mass remained significantly associated with femoral neck BMD (β = 0.49, p <0.001), spine BMD (β = 0.48, p< 0.0001) and hip BMD (β = 0.59, p< 0.0001). Lean mass was also negatively associated with fracture risk (β = -0.19 p =0.04) when both lean and fat mass were in the same model. Study 3: After adjusting for age, body fat, habitual physical activity, tobacco use and season, neither 25(OH)D nor PTH concentrations showed significant associations with having the metabolic syndrome. However, when body fat was replaced with waist circumference there was a weak positive association between 25(OH)D concentration and the metabolic syndrome. No significant association was found between PTH:25(OH)D ratio and the metabolic syndrome. Conclusion This thesis has highlighted that the prevalence of obesity among black South Africans is high particularly among women and urbanization played a significant role in the increasing adiposity of black South Africans in the North West province. Lean mass had a stronger association with bone health in comparison to fat mass in urban black South African women. Low 25(OH)D concentration was not associated with the metabolic syndrome while there was no significant association between PTH and the metabolic syndrome in our black South African women. / PhD (Dietetics), North-West University, Potchefstroom Campus, 2015

Metabolic syndrome affects approximately 25% of the US population and increases risk for the development of cardiovascular disease, as well as, and Type 2 diabetes. Inorganic arsenite exposure has been associated with cardiovascular disease, insulin resistance and Type 2 diabetes. The mechanisms by which arsenic increases these health risks has not been fully elucidated. In this report we show two pathways by which arsenite may contribute to metabolic syndrome. First through induction of C-Reactive Protein (CRP) and secondly through inhibition of insulin stimulated glucose uptake. CRP is a clinical marker for metabolic syndrome and a predictive clinical marker for cardiovascular disease and type 2 diabetes. Treatment of HepG2 cells with arsenite resulted in elevated CRP production and secretion. In addition, treatment of FvB mice with 100 ppb sodium arsenite via drinking water for six months starting at weaning age resulted in dramatically higher levels of CRP in both the liver and inner medullary region of the kidney. Further, mouse Inner Medullary Collecting Duct cells (mIMCD-3), a mouse kidney cell line, were stimulated with CRP, which resulted in activation of NFkappaB. Pretreatment with Y27632, a Rho kinase inhibitor, prior to CRP stimulation attenuated NFkappaB activation. Additionally, L6 myocytes, an insulin responsive cell line, exposed to arsenite for 4 or 7 days showed decreased insulin-stimulated glucose uptake but no decrease in AKT activation. In addition, we found that ERK activity decreased, while p38 MAPK activity increased, in response to prolonged arsenite treatment. These data support the epidemiological evidence that chronic exposure to low physiologically relevant levels of arsenite can contribute to insulin resistance and type 2 diabetes. These data provide a novel pathway by which arsenic can contribute to metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes.

Disertacijoje tyrinėjami moterų antropometriniai ir medžiagų apykaitos pokyčiai nėštumo metu ir praėjus 20 metų po gimdymo. Pagrindinis darbo tikslas – įvertinti moterų antropometrinius ir medžiagų apykaitos pokyčius, įvykusius per 20 metų bei įvertinti metabolinio sindromo ilgalaikės rizikos sąsajos su moterų kūno sandaros ir medžiagų apykaitos pokyčiais, įvykusiais dar buvusių nėštumų metu. Tyrimo rezultatai parodė, kad per 20 metų tiriamosioms vystosi nepalankus kūno sandaros pokyčiai (kūno masės, KMI padidėjimas, riebalinio audinio centralizacijos tendencija) ir medžiagų apykaitos pokyčiai (proaterogeninio pobūdžio dislipidemiją, padidėjusia serumo gliukozės koncentracija bei padidėjęs atsparumas insulinui). Tyrimas taip pat atskleidė ankstyvuosius kūno sandaros skirtumus tarp sveikųjų ir metaboliniu sindromu sergančiųjų moterų. Pasiūlyti du antropometriniai rodikliai, kurie galėtų padėti prognozuoti ilgalaikę metabolinio sindromo išsivystymo riziką - santykinis žasto trigalvio raumens klostės pokytis ir absoliučiojo pasyviosios kūno masės prieaugio nėštumo laikotarpiu santykis su naujagimio gimimo mase. Be to, tyrime įvertintas kraujo serumo adipokinų koncentracijos ir jų išvestinių rodiklių ryšys su moterų fiziologinėmis ir patologinėmis būklėmis. / This work research is the longest known research of observing the body structure and metabolic changes in women during pregnancy and 20 years after it. Tasks of work – to assess the changes in the anthropometric and metabolic parameters in women within twenty years; to assess the relations of a long-term risk of metabolic syndrome with the body composition and metabolic changes in women had happened during their previous pregnancies. The research data show unfavourable long-term changes in the women’s body structure parameters (body mass and BMI increased, adipose tissue centralization was determined) and metabolic parameters (a proatherogenic dyslipidaemia, the glucose concentration increased and resistance of insulin increased). The work data show the first body markers were already detected during pregnancy for the women who had the metabolic syndrome at the end of the research. We found two anthropometric indicators which could help to prognosticate a long-time risk of the development of metabolic syndrome the relative change in the triceps skin fold and the ratio between the absolute growth in the passive body mass during pregnancy and the neonate’s birth mass. Besides, the research assessed the relation of the adipokines profile parameters with physiological and pathological conditions in women.

This work research is the longest known research of observing the body structure and metabolic changes in women during pregnancy and 20 years after it. Tasks of work – to assess the changes in the anthropometric and metabolic parameters in women within twenty years; to assess the relations of a long-term risk of metabolic syndrome with the body composition and metabolic changes in women had happened during their previous pregnancies. The research data show unfavourable long-term changes in the women’s body structure parameters (body mass and BMI increased, adipose tissue centralization was determined) and metabolic parameters (a proatherogenic dyslipidaemia, the glucose concentration increased and resistance of insulin increased). The work data show the first body markers were already detected during pregnancy for the women who had the metabolic syndrome at the end of the research. We found two anthropometric indicators which could help to prognosticate a long-time risk of the development of metabolic syndrome the relative change in the triceps skin fold and the ratio between the absolute growth in the passive body mass during pregnancy and the neonate’s birth mass. Besides, the research assessed the relation of the adipokines profile parameters with physiological and pathological conditions in women. / Disertacijoje tyrinėjami moterų antropometriniai ir medžiagų apykaitos pokyčiai nėštumo metu ir praėjus 20 metų po gimdymo. Pagrindinis darbo tikslas – įvertinti moterų antropometrinius ir medžiagų apykaitos pokyčius, įvykusius per 20 metų bei įvertinti metabolinio sindromo ilgalaikės rizikos sąsajos su moterų kūno sandaros ir medžiagų apykaitos pokyčiais, įvykusiais dar buvusių nėštumų metu. Tyrimo rezultatai parodė, kad per 20 metų tiriamosioms vystosi nepalankus kūno sandaros pokyčiai (kūno masės, KMI padidėjimas, riebalinio audinio centralizacijos tendencija) ir medžiagų apykaitos pokyčiai (proaterogeninio pobūdžio dislipidemiją, padidėjusia serumo gliukozės koncentracija bei padidėjęs atsparumas insulinui). Tyrimas taip pat atskleidė ankstyvuosius kūno sandaros skirtumus tarp sveikųjų ir metaboliniu sindromu sergančiųjų moterų. Pasiūlyti du antropometriniai rodikliai, kurie galėtų padėti prognozuoti ilgalaikę metabolinio sindromo išsivystymo riziką - santykinis žasto trigalvio raumens klostės pokytis ir absoliučiojo pasyviosios kūno masės prieaugio nėštumo laikotarpiu santykis su naujagimio gimimo mase. Be to, tyrime įvertintas kraujo serumo adipokinų koncentracijos ir jų išvestinių rodiklių ryšys su moterų fiziologinėmis ir patologinėmis būklėmis.