Browsing by Author "Goedecke, Julia"

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    Accuracy of reporting food energy intake: Influence of ethnicity and body weight status in South African women
    (2010) Mchiza, Z J; Goedecke, Julia; Lambert, Estelle
    The current study sought to identify characteristics that may be associated with the misreporting of food energy intake (EI) in urban South African women. A total of 198 women (61 black, 76 of mixed ancestry, 61 white) completed a quantified food frequency questionnaire, from which daily energy and macronutrient intake were calculated. Body composition (body mass index [BMI], percentage of body fat), body image (Feel-Ideal Difference index and Body Shape questions) and socio-economic status (SES) (household density and asset index) were also measured. Food EI in relation to estimated basal metabolic rate ratio that was less than 1.05 represented under-reporting, whereas a ratio greater than 2.28 represented over-reporting. Results suggested that 26% of the participants under-reported, 64% adequately reported and 10% over-reported. Participants who under-reported had a higher BMI (p < 0.01) and higher percentage of body fat (p < 0.05) than those who adequately and over-reported. The majority of under-reporters were black (38%) versus 21% under-reporters of mixed ancestry and 20% white under-reporters (p < 0.01). Eighty-three per cent of black under-reporters were obese. On the other hand, a majority (63%) of overweight women of mixed ancestry and a majority (50%) of white normal-weight women under-reported their food EI. Under-reporters reported a lower intake of dietary fat (p < 0.01) and a higher intake of dietary protein (p < 0.01) than adequate or over-reporters. Food EI reporting was not influenced by SES or body image. In conclusion, results suggest that food EI reporting is influenced by body size, and may be ethnic-specific in South African women.
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    Depot differences in adipose tissue metabolism and function in obese black South African women and changes in response to an exercise training intervention
    (2020) Nono Nankam, Pamela Arielle; Goedecke, Julia
    Black South African (SA) women are disproportionally affected by obesity and insulin resistance, which have been associated with depot-specific alterations in adipose tissue function. This thesis aimed to evaluate the differences in fatty acid (FA) composition and gene expression between abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT), and the changes in response to exercise training in relation to body composition, hepatic fat, inflammatory and oxidative stress markers, and insulin sensitivity (SI) in obese black SA women. This research evaluated the i) FA composition of aSAT and gSAT, and red blood cell total phospholipids (RBC-TPL) and their associations with body composition, hepatic fat and SI, ii) changes in these FA profiles in response to exercise training and the relationship with changes in systemic inflammation, hepatic fat and SI; iii) effects of exercise training on systemic markers and SAT gene expression of inflammation and oxidative stress; and iv) regional differences in transcriptome profiles of aSAT and gSAT pre- and post-exercise training. Forty-five IsiXhosa women (30-40kg/m2 , 20-35 years) were randomized into control (n=22) or exercise groups (n=23; 12-week aerobic-resistance training, 40-60 min/session, 4 days/week). Pre and postintervention measurements included: anthropometry, body composition, cardiorespiratory fitness, dietary intake, SI, hepatic fat, systemic markers and SAT gene expression of adipokines, inflammation and oxidative stress, RBC-TPL and SAT fatty acids profiles, and untargeted SAT gene expression analyses. The main findings showed differences in the circulating (RBC-TPL) and stored (SAT) FA composition, which reflected in different associations between these FA profiles and SI. Moreover, the changes in FA composition in response to exercise training were depot-specific, with the changes in RBC-TPL correlating with a decrease in systemic inflammation and hepatic fat. Exercise training alleviated systemic oxidative stress and induced increased gSAT inflammatory genes, reflecting SAT remodelling. These changes coincided with a reduction in gynoid fat and were not associated with increased SI. Furthermore, there were unique depot-specific gene expression signatures relating to embryonic development at baseline and more diverse functional-related processes at post-training. This generated novel candidate genes potentially implicated in the relationship between body fat distribution and metabolic status in obese black SA women.
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    Dietary fat modulates the relationship between polymorphisms in the TNFA and IL-6 genes, and obesity and serum lipid concentrations in black and white South Afican women
    (2013) Joffe, Yael; Goedecke, Julia; Collins, Malcolm; Van der Merwe, Lize
    The primary aim of the thesis was to investigate associations between TNFA (TNFA-308 G>A and -238 G>A) and IL-6 (-174 G>C, IVS3+281 G>T, IVS4+869 A>G) sequence variants and obesity and serum lipid concentrations in black and white SA women. This included identifying sequence variants in the IL-6 gene with a reported high heterozygosity in both the white and black SA populations (rs1554606 and sr2069845). Dietary intake data of adequate reporters was then included in the analysis to investigate whether dietary fatty acid intake modulated the interactions between the TNFA and IL-6 SNPs (TNFA -308 G>A and -238 G>A & IL-6 -174 G>C, IVS3+281 G>T, IVS4+869 A>G) and obesity, measures of adiposity and serum lipid concentrations, and whether interactions identified differed between black and white women.
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    Effects of adipose tissue extracellular matrix components on body fat distribution and insulin sensitivity in black and white South African women
    (2018) Kotzé-Hörstmann, Liske; Goedecke, Julia; Keswell, Dheshnie
    The global burden of non-communicable diseases (NCD’s) is unacceptably high and disproportionately affects developing countries such as South Africa (SA). Black SA women have a higher prevalence of obesity and a greater associated risk for developing metabolic diseases (such as type 2 diabetes mellitus) than their white counterparts. An improved understanding of the ethnic-specific mechanisms underlying the increased risk of T2DM in black SA women is needed to inform future studies aimed at reducing the prevalence of this diseases. One of the major determinants of insulin resistance is android/central body fat partitioning, with visceral adipose tissue (VAT) enlargement, in particular, being closely associated with increased risk. Conversely, lower-body fat accumulation is considered to be protective. However, these relationships between body fat distribution and its metabolic effects are altered by ethnicity. Black SA women have less abdominal and greater gluteal-femoral subcutaneous adipose tissue (SAT) but are more insulin resistant compared to BMI- and waist circumference-matched white SA women. A similar profile has been described in black African-American women. The reduced protective effect of peripheral fat distribution in black women remains to be understood. The primary aim of this thesis was positioned within the context of adipose tissue expandability hypothesis, and aimed to examine the hypothesis that differences in SAT extracellular matrix (ECM)- and hypoxia-related gene expression and their ethnic specific associations with body composition and insulin sensitivity may explain, in part, the higher rates of insulin resistance in black compared to white South African women. Therefore, it was hypothesized that, as a consequence of increased adipose tissue hypertrophy in the gluteal depot of obese black compared to obese white women, gluteal SAT adipose tissue hypoxia and ECM component gene expression is higher in black compared to white women, and associates with their reduced insulin sensitivity (SI) and higher insulin response. In order to address this hypothesis, four research studies were designed. The first study (Chapter 3) in this thesis aimed to compare depot-specific (abdominal vs. gluteal) expression of hypoxia and ECM genes in normal-weight and obese black and white women, and to examine the ethnic-specific associations between these genes and body composition, measures of insulin sensitivity and secretion and inflammatory gene expression in black and white SA women by using a gene expression (Reverse transcription polymerase chain reaction (RT-PCR)) analysis. This thesis showed for the first time that hypoxia inducible factor 1 (HIF-1α), collagen type V α1 (Col5A1) and type VI α1 (COL6A1) gene expression were higher in the gluteal, but not the abdominal SAT depots, of black compared to white women, and associated with reduced insulin sensitivity in black women only. The expression of the hypoxia and ECM genes associated with inflammatory gene expression in both the gluteal and abdominal SAT depots of black women, whereas the expression of these genes associated with the inflammatory gene expression mostly in the abdominal SAT depots of white women. The second study (Chapter 4) tests the hypothesis that higher hypoxia and ECM related gene expression would associate with higher central fat mass accumulation in black women and that the expression of these genes may be associated with changes in the measures of insulin sensitivity in black and white women. Thus, this longitudinal study aimed to determine whether changes in body composition and insulin sensitivity variables over a 5 year follow-up period associated with variations in hypoxia and ECM related gene expression in the gluteal SAT of black and white women. Over the 5-year follow-up period, increased body fat mass in white women associated with increased PPARγ mRNA expression whereas increased body fat mass in black women associated with lower COL5A1 expression. Furthermore, HIF-1α, and COL6A1 expression correlated positively with the change in fasting insulin concentrations in black but not in white women. It is not clear whether high circulating insulin may directly increase HIF-1α expression and contribute to the formation of excess ECM, or whether increased insulin may simply be a concomitant downstream effect of increased insulin resistance, as a consequence of increased fibrosis and the generation of inflammation. By using a cell culture based study, the third study in this thesis (chapter 5), investigated the effects of increasing insulin concentrations on the expression of hypoxia and ECM related genes under normoxic and hypoxic conditions in mature 3T3-L1 adipocytes. It was found that insulin and hypoxia treatment significantly elevated HIF-1α mRNA and protein levels but that the observed effects were not additive. Further, hypoxia, but not insulin treatment, increased the expression of Col5a1 and Col6a1 protein but not mRNA levels in mature 3T3-L1 adipocytes. By using a genotyping analysis, the fourth study (Chapter 6) aimed to determine whether variants within two ECM component gene polymorphisms, collagen type 5α1 (COL5A1) rs12722 (C/T) and type 6α1 (COL6A1) rs35796750 (C/T) associates with body fat distribution and insulin resistance in black and white women. Allele and genotype distributions of the COL5A1 rs12722 and COL6A1 rs35796750 polymorphisms, as well as body fat distribution were significantly different between black and white women, the T- variant of the COL5A1 rs12722 polymorphism was associated with significantly less central fat mass, characterised by a smaller waist circumference and lower VAT, and this effect was independent of ethnicity. In addition, T- variant of the COL5A1 rs12722 polymorphism was associated with lower fasted insulin concentrations and HOMA-IR in white but not in black women. In contrast, no genotype associations between COL6A1 rs35796750 and any of the body fat mass, its distribution and insulin resistance measures in black or white women were reported. This thesis used a hypothesis driven approach to provide preliminary evidence that the gluteal depot of obese black women has higher expression of hypoxia and ECM genes compared to that of obese white women and provides novel insight into the apparent paradox of reduced insulin sensitivity despite lower VAT and greater peripheral SAT accumulation in black compared to white women. An improved understanding of the ethnic-specific mechanisms underlying the increased risk of T2DM in black SA women will enable the development of cost-effective preventative care strategies within the South African demographic
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    Ethnic specific associations between body composition and metabolic risk and the role of sex hormones and aromatase among black and white South African women
    (2015) Tootla, Mehreen; Goedecke, Julia; Keswell, Dheshnie
    Background: Previous evidence has demonstrated ethnic differences in the relationship between body fat distribution and metabolic risk between black and white women. However, the reasons for these differences are not known and may be explained in part by differences in sex hormones. The overall aim of this thesis was therefore to i) examine ethnic-specific associations between body fat and its distribution and cardio-metabolic outcomes (study 1) and ii) examine the associations between sex hormones and subcutaneous adipose tissue (SAT) expression of oestrogen receptors (ERα and ERβ) and aromatase (CYP19A), and body fat distribution and insulin resistance (IR) among black and white women (study 2).Methods: Study 1: In 288 black and 197 white premenopausal women, dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) derived measures of body fat distribution and cardio-metabolic factors including IR (HOMAIR) and lipid levels were measured. Study 2: In a subsample consisting of 13 normal-weight and 15 obese black and 15normal-weight and 12 obese white women, HOMAIR and SI (frequently sampled intravenous glucose tolerance test) and ERα, ERβ and CYP19A gene expression were measured in abdominal and gluteal SAT. Results: Study 1: Compared to white women, black women had less central and greater lower body fat, but had similar IR and lower serum lipid concentrations. Despite these differences, the associations between body fat distribution and measures of IR, as well as TG and HDL-Concentrations were similar in black and white women. Notably, central and peripheral fat deposition was independently associated with IR in both the black and white women, and with TG in the black women. In contrast, the associations between body composition and fasting plasma glucose, TC and LDL-C concentrations differed between black and white women. Fasting glucose concentrations were associated with centralisation of body fat in black but not white women, whereas TC and LDL-C concentrations were associated with centralisation of body fat in white but not black women. In addition to body fat distribution, MVPA was associated with IR in the white women, and contraception use was associated with lipid levels in the black and white women. Study 2: CYP19A expression was positively associated with increased adiposity in black and white women in all three depots. Gluteal ERα was significantly higher and ERβ was significantly lower in the black compared to the white women, irrespective of BMI. Gluteal ERα was negatively associated with trunk fat mass (FM) and HOMAIR in the black women only. Gluteal ERα was significantly lower in obese white compared to normal weight white women. Additionally oestradiol (E2) levels were lower in obese compared to normal-weight white women, but did not differ by ethnicity. Conclusion: Our results indicate that it is important in both black and white populations, to decrease centralisation of body fat. Modifiable risk factors such as MVPA and contraception use should be used as therapeutic targets to prevent and manage CVD. Additionally, oestrogen receptors may be an important determinant of body fat distribution and risk in the black women.
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    Ethnic-specific associations between abdominal and gluteal fat distribution and the metabolic complications of obesity : implications for the use of liposuction
    (2011) Hayes, Philip Michael; Goedecke, Julia
    More than three-quarters (77%) of the 40.5 million people living in South Africa are black African, of which more than 40% are urbanised. Black African women living in urban areas have a significantly higher prevalence (62%) of overweight than urban black males (28%) or white females (53%). It was previously thought that obesity in black South African women was not associated with deleterious metabolic sequelae and was termed "healthy" obesity...
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    Fasting substrate oxidation in relation to habitual dietary fat intake and insulin resistance in non-diabetic women: a case for metabolic flexibility?
    (BioMed Central Ltd, 2013) Carstens, Madelaine; Goedecke, Julia; Dugas, Lara; Evans, Juliet; Kroff, Jacolene; Levitt, Naomi; Lambert, Estelle
    BACKGROUND: Metabolic flexibility described as "the capacity of the body to match fuel oxidation to fuel availability" has been implicated in insulin resistance. We examined fasting substrate oxidation in relation to dietary macronutrient intake, and markers of insulin resistance in otherwise healthy women, with and without a family history of diabetes mellitus (FH DM). METHODS: We measured body composition (dual x-ray absorptiometry), visceral and subcutaneous adipose tissue area (VAT, SAT, using Computerised Tomography), fasting [glucose], [insulin], [free fatty acids], [blood lipids], insulin resistance (HOMA-IR), resting energy expenditure (REE), respiratory exchange ratio(RER) and self-reported physical activity in a convenience sample of 180 women (18-45 yrs). A food frequency questionnaire was used to assess energy intake (EI) and calculate the RER: Food Quotient (FQ) ratio. Only those with EI:REE (1.05 -2.28) were included (N=140). Insulin resistance was defined HOMA-IR (>1.95). RESULTS: The Insulin Resistant (IR) group had higher energy, carbohydrate and protein intakes (p<0.05) and lower PA levels than Insulin Sensitive (IS) group (P<0.001), but there were no differences in RER or RER:FQ between groups. However, nearly 50% of the variance in HOMA-IR was explained by age, body fat %, VAT, RER:FQ and FH DM (adjusted R2=0.50, p<0.0001). Insulin-resistant women, and those with FH DM had a higher RER:FQ than their counterparts (p<0.01), independent of body fat % or distribution. CONCLUSION: In these apparently healthy, weight-stable women, insulin resistance and FH DM were associated with lower fat oxidation in relation to dietary fat intake, suggesting lower metabolic flexibility.
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    The impact of body fat and its distribution on risk factors for cardiovascular disease in black South African women
    (2008) Jennings, Courtney L; Goedecke, Julia; Collins, Malcolm
    Obesity and obesity-related diseases are a large global problem in both developed and developing nations. In South Africa, a country currently undergoing epidemiological transition, the prevalence of obesity is high, particularly in urban black women. Early detection of overweight and obese individuals is essential for the management of obesity and its related co-morbidities; however, there is no ethnic-specific field measure of body fat percent validated for use in black South African women. Further, despite high levels of adiposity, these women have an atypical presentation of cardiovascular disease (CVD) risk factors, presenting with relatively low levels of visceral adipose tissue (VAT) and a favourable lipid profile compared to white women. As a result of this atypical presentation of CVD risk factors, a high prevalence of “healthy obesity” has been reported, although the determinants of this phenotype have not been systematically investigated. In addition, the applicability of commonly used diagnostic criteria for the determination of insulin resistance, which include enlarged waist circumference and dyslipidemia as components, has not been investigated in this population. Therefore, the overall aim of this thesis was to investigate the impact of body fat and its distribution on the presentation and identification of CVD risk factors in relatively young black South African women, prior to the onset of CVD. More specifically, the objectives were; i) to determine if near infrared interactance (NIR) is a valid field measure of body fat percent in South African women; ii) to determine the agreement between International Diabetes Federation (IDF) and National Cholesterol Education Program (Adult treatment panel III) (ATP III) metabolic syndrome criteria and the degree to which these criteria can predict insulin resistance, and explore the extent to which these phenomena can be explained by body fat and its distribution; iii) to identify determinants of the “metabolically healthy obese” (MHO) and “metabolically obese normal weight” (MONW) phenotypes; and iv) to complete a preliminary investigation of the association between polymorphisms within genes that encode for proteins involved in tissue-specific glucocorticoid metabolism and obesity, body fat distribution and CVD risk factors in black South African women. As obesity is associated with increased risk of cardiovascular disease, accurate quantification of body fatness is particularly important in health risk appraisal. However, in developing countries, “gold standard” measures of body fat percent such as underwater weighing and dual energy x-ray absorptiometry (DXA) are not always practical, as access to facilities and resources are limited. Therefore, a valid field measure of body fat percent is needed for the purpose of health risk appraisal. NIR is a potentially useful field measure of body fat percent that is currently used in South Africa for this purpose. However, NIR cannot be used with confidence in South Africa until it has been validated in different ethnic populations. Therefore, the first study in this thesis examined the validity of singlesite NIR (Futrex-6100 A/ZL) as a measure of body fat percent compared to the criterion method of DXA in black and white South African women.
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    The impact of obesity and inflammation on metabolic risk factors for cardiovascular disease and type two diabetes in black and white South African women
    (2011) Evans, Juliet P; Goedecke, Julia; Tommy Olsson
    [T]he overall aim of this thesis was to investigate the ethnic-specific role of inflammation in obesity and related metabolic risk factors associated with T2DM and CVD in apparently healthy black and white premenopausal South African women.
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    Intra-familial and ethnic effects on attitudinal and perceptual body image: a cohort of South African mother-daughter dyads
    (BioMed Central Ltd, 2011) Mchiza, Zandile; Goedecke, Julia; Lambert, Estelle
    BACKGROUND: International studies suggest ethnic differences in obesity prevalence may be due, in part, to differences in body image and body size dissatisfaction between groups. Further, there is evidence to suggest that there is a familial resemblance in body image between mothers and their younger (preadolescent) daughters. This research was therefore conducted to specifically identify the extent to which family status (presented as mother-daughter resemblance) and ethnicity impact on body image attitudes and perceptions of South African mothers and their pre-adolescent daughters. METHODS: Mother-daughter dyads (n = 201, 31% black, 37% mixed ancestry and 32% white) answered questions regarding their body image perception (the way they saw their body size status), their body image ideals, and body image attitudes (body size dissatisfaction in particular, presented as the Feel-Ideal Difference [FID] index score). Mothers' and daughters' body image results were compared within dyads and across ethnic groups using repeated measures of ANOVA. RESULTS: Overall, body image resemblances exist between South African mothers and their pre-adolescent daughters. Mothers and daughters chose similarly weighted silhouettes to represent their body size ideals (p = 0.308), regardless of their ethnicity or body mass index (BMI). The FID index scores were similar between mothers and their daughters only after the confounding effects of maternal BMI were removed (p = 0.685). The silhouettes chosen to represent thinness were also similar between mothers and their daughters (p = 0.960) regardless of ethnicity and maternal BMI. On the other hand, the silhouettes chosen to represent fatness were similar (p = 0.342) between mothers and their daughters, only after the confounding effects of maternal BMI were removed. Lastly, mothers and their daughters chose similarly weighted silhouettes as engendering feelings of beauty, respect and happiness (p = 0.813; p = 0.615 and p = 0.693, respectively). In this instance, black mother-daughter dyads chose significantly heavier silhouettes than the other ethnic groups. This implies that black mothers and daughters associate beauty, respect and happiness with a bigger body size. CONCLUSION: Resemblances exist between pre-adolescent girls and their mothers on issues related to ideal and attitudinal body image. In this regard, South African researchers should consider the effects ethnicity and family status on body image of women when developing targeted interventions to prevent or manage obesity.
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    The effect of an exercise intervention on insulin sensitivity, insulin secretion and insulin clearance in black obese South African women
    (2020) Fortuin-De Smidt, Melony; Goedecke, Julia; Mendham, Amy
    Introduction: Black African populations present with low insulin sensitivity (SI) and hyperinsulinemia, the latter due to high insulin secretion and reduced clearance. In addition, they exhibit lower levels of central and ectopic fat, compared to their white counterparts, contradicting the known correlates of SI typically reported in white populations. Moreover, in black African women hyperinsulinemia is in excess of the level needed to compensate for low SI, with a corresponding high disposition index (DI), a marker of insulin response that accounts for the level of SI. Further, obese, black African women have a high risk for type 2 diabetes (T2D), but the correlates of hyperinsulinemia have not been fully elucidated, especially the role of ectopic fat and body fat distribution. Exercise training is beneficial to improve SI and DI, however, whether these effects are mediated by changes in ectopic fat in skeletal muscle, liver and pancreatic depots is unknown. Accordingly, exercise training can be used as a model to assess the correlates of hyperinsulinemia and SI in cohorts at high risk for developing T2D, such as obese black African women. This thesis therefore aims to describe the correlates of hyperinsulinemia and SI and to evaluate the effect of exercise training on these components with emphasis on the role of body fat distribution and ectopic fat in mediating these changes. Methods: Firstly, a cross-sectional analysis of 45 obese (BMI 30-40 kg/m2 ) black South African women (age 20-35 years) without T2D was conducted. Thereafter the women were block randomized into an exercise training (n=23) or no exercise (control, n=22) group. The exercise training group participated in a 12-week combined aerobic and resistance training programme (40-60 min session, 4 days/week) supervised by a biokineticist. Pre and post-intervention testing included assessment of acute insulin response to glucose (AIRg), SI, DI (AIRg x SI), insulin secretion rate (ISR), hepatic insulin extraction (HIE) and peripheral insulin clearance (CLp) (frequently sampled intravenous glucose tolerance test); body fat mass and regional adiposity (dual-energy X-ray absorptiometry); hepatic, pancreatic and skeletal muscle fat and abdominal subcutaneous (aSAT) and visceral adipose tissue (VAT) (magnetic resonance imaging); intramyocellular (IMCL) and extramyocellular fat content (EMCL) (magnetic resonance spectroscopy). Results: The baseline results showed that a high DI was associated with low VAT (r0.565, p< 0.001), pancreatic fat, soleus IMCL and EMCL with VAT explaining most of the variance in DI (32%). SI was inversely associated with VAT (rho -0.417, p=0.007) and AIRg was inversely and HIE was positively associated with VAT-aSAT ratio (rho - 0.345, p=0.029 and rho 0.510, p=0.011, respectively). DI was positively associated with CLp (rho 0.528, p=0.006), while its components (SI and AIRg) were not. Results from the intervention showed that exercise training increased DI (median (interquartile range): 6.1 (3.6-7.1) to 6.5 (5.6-9.2) x103 arbitrary units, p=0.028), SI (2.0 (1.2-2.8) to 2.2 (1.5-3.7) (mU/l) -1 min -1 , p=0.005) and VO2peak (mean ± standard deviation: 24.9±2.42 to 27.6±3.39 ml/kg/min, p< 0.001), with no changes in control group. Exercise training decreased body weight (84.1±8.7 to 83.3±.9.7 kg, p=0.038) and gynoid fat mass (18.5±1.7 to 18.2±1.6%, p< 0.001). AIRg, ISR, HIE, CLp, aSAT, VAT and ectopic fat were unchanged after exercise training. However, the control group increased body weight and aSAT. The increase in SI and DI were not associated with changes in body composition, body fat distribution or ectopic fat. Conclusion: Novel results from our cross-sectional analysis showed that, in obese black South African women, DI was positively associated with peripheral insulin clearance, probably due to higher SI of peripheral tissue. Moreover, the most important correlate of a high DI was low VAT independent of ectopic fat accumulation in other sites. Further, we showed that low AIRg and high HIE correlated with a high VAT-aSAT ratio, while low SI was associated with high VAT. These associations require further exploration to determine direction of causality. Findings from our exercise intervention study extend on previous research by showing that moderate-to-high intensity combined aerobic and resistance exercise training increased SI and improved cardiovascular fitness, but insulin secretion, hepatic insulin clearance, ectopic and central fat depots did not change. Our results suggest that hyperinsulinemia may not occur solely as a compensatory mechanism for low SI and that ectopic and central fat might not be the primary correlates of insulin resistance in this cohort. Rather, intrinsic factors within muscle and adipose tissue may be putative mediators for observed improvements in the metabolic outcomes but will require further elucidation. Further research is required to confirm the causal role of VAT on low DI and to determine whether a long-term exercise training program and/or a low carbohydrate/glycemic index diet will reduce AIRg in those with hyperinsulinemia.
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    The role of metabolic rate and substrate utilization in the maintenance of body weight, body composition and insulin sensitivity
    (2019) Clamp, Louise Diana; Kroff, Jacolene; Goedecke, Julia
    Obesity treatment requires approaches that target the reduction of body weight and fat mass. The improvement of cardiorespiratory fitness (CRF), metabolic flexibility and insulin sensitivity also contribute towards reducing obesity-associated risk factors. While energy restriction alone results in significant weight loss, exercise-only interventions provide small amounts of weight loss and prevent weight gain, while also improving many of the other variables targeted in obesity treatment. Once achieved however, successful weight-loss maintenance is challenging, with many individuals subsequently experiencing weight regain. The main objectives of this thesis were to explore the role of metabolic rate and substrate utilization in influencing body weight, body composition and insulin sensitivity. This twopart thesis hypothesised that: 1) exercise training, without dietary intervention, will improve metabolic rate and substrate utilization in a sedentary obese population, and that this would be associated with improved body composition, insulin sensitivity and CRF; and 2) metabolic rate, substrate utilization and insulin sensitivity are altered through weight loss/regain, predisposing these individuals to weight regain and impairing successful weight-loss maintenance. In Part 1 of this thesis a 12 week exercise intervention in sedentary, obese (BMI 30-40kg.m-2 ) black South African (SA) women (aged 22, IQR 21-24 years) was completed. Previous studies have shown that black SA women present with very low CRF, a key indicator of increased risk for non-communicable disease (NCD), and have a high prevalence of obesity and insulin resistance (IR). They are thus at increased risk for developing type 2 diabetes (T2DM). Furthermore, physiologically black SA women have also been shown to have less visceral adipose tissue (VAT) and more peripheral gluteal fat mass (FM) compared to their white counterparts, but are paradoxically more IR. Despite this presentation, to date there has been no supervised exercise intervention studies undertaken in this very high risk population group. The first study of this thesis (chapter 2) aimed to assess the effects of the exercise intervention on changes in CRF, energy expenditure (EE) and substrate utilization, both at rest and during steady-state exercise compared to non-exercising controls. It also assessed baseline and changes in these measurements in relation to changes in body composition. Black SA women (BMI 30-40 kg.m-2 , 20-35 y) were recruited and randomized into control (CTL, n=15), or exercise (EXE, n=20) groups. The CTL was instructed to maintain usual activity while the EXE completed 12 weeks of combined resistance and aerobic exercise training (4d.wk-1 , 40-60min.d-1 @ >70% peak heart rate (HRpeak)). At pre-intervention, a treadmill-based CRF test, measuring peak volume of oxygen consumption (VO2peak), was carried out. Thereafter resting and steady state exercise (50% VO2peak) energy expenditure (EE) and respiratory exchange (RER) were measured along with body composition (dualenergy X-ray absorptiometry (DXA)). A frequently sampled intravenous glucose tolerance test (FSIGT) was also carried out to determine changes in insulin sensitivity. These tests were repeated at post-intervention testing with steady state testing being carried out both at the same relative intensity (50% post-testing VO2peak) and the same workload (treadmill speed and gradient) as used for pre-testing. Dietary intake (4d diary) and daily step-count (ActivPAL) data was collected at pre-testing, 4, 8 & 12 weeks. Results showed that all participants had very low baseline CRF, falling below the 20th percentile previously shown in African American women. In response to exercise training, CRF increased by ≈11% and rates of fat oxidation during steady-state exercise were improved, while in controls these remained unchanged. Compared to CTL, EXE also showed small but significant reductions, in weight, as well as BMI, waist (WC) and hip (HC) circumferences. In contrast weight, BMI and WC increased in non-exercising controls. Gynoid FM (absolute FM and as a proportion of total FM), rather than visceral adipose tissue (VAT), was reduced in exercise participants. Within the exercise group higher baseline fat oxidation rates during steady state exercise and lower resting carbohydrate oxidation rates explained 61.6% (p< 0.001) of the variability in changes in gynoid FM in response to 12 weeks of exercise training in this group. In conclusion, exercise training improved CRF and fat oxidation rates during submaximal exercise in sedentary, obese black SA women. Higher fat oxidation rates during steady state exercise and lower resting carbohydrate oxidation rates at baseline were associated with the mobilization of gynoid FM in response to exercise training, rather than VAT as is typically shown in exercise interventions. This novel finding potentially represents an ethnic/gender specific response to exercise training. Further studies are needed to confirm this. Similar exercise training programs, that are sustainable over the long term, would therefore be beneficial in achieving meaningful increases in CRF while also supporting weight management and body composition improvements in this high risk population group. Using data from the exercise intervention in obese black SA women, the second study of this thesis (chapter 3) investigated inter-individual variability in the CRF response (∆VO2peak) to exercise training. The study specifically aimed to compare changes in EE and substrate utilization at rest and during steady state exercise, body weight and composition and insulin sensitivity between high and low CRF responders to the 12 week intervention. Furthermore it aimed to explore associations between baseline metabolic rate, EE and substrate utilization and subsequent changes in CRF in response to exercise training, to determine if baseline variability in these measures contributed to inter-individual variability in the CRF outcome. Within the exercise group, high inter-individual variability in CRF response to exercise training was identified. Based on a median split in ∆VO2peak, high responders (HRS, n=10) increased CRF by 21.7 ±10.0% (p< 0.001) compared to no change in both low responders (LRS, n=10; +0.6 ±6.3%, p=0.748) and CTL (-3.2 ±10.8%, p=0.195). This occurred despite all groups having similar baseline VO2peak and the exercise group receiving the same exercise dose (number of exercise sessions attended and average intensity of the exercise sessions). At baseline, HRS derived ≈62% of energy expenditure from fat oxidation during steady-state exercise compared to just 41% in LRS, who relied to a greater extent on carbohydrate oxidation. Furthermore, HRS were ≈11 kg lighter than LRS. There was also a positive association between BMI and RER such that individuals with higher BMI showed lower fat utilization (i.e., higher RER). HRS reduced gynoid FM whereas in LRS this remained unchanged. This is in line with the findings of the previous chapter which showed that exercise-related reduction in gynoid FM was associated with greater baseline fat oxidation. LRS showed improvements in insulin sensitivity compared to CTL and HRS. Using regression analysis including the exercising participants, greater baseline carbohydrate oxidation rates both at rest and during steady state exercise predicted a poorer CRF to exercise training, explaining 37.5% of the variability in ∆VO2peak. To the best of my knowledge, this is the first study to show that baseline variability in substrate utilization among sedentary obese individuals contributes towards explaining the variability in the CRF response to exercise training. However, further studies are required to confirm these results. Together, these studies show that higher fat oxidation rates are necessary for FM mobilization, while correspondingly reduced reliance on carbohydrate oxidation both at rest and during exercise supports improvements in CRF in response to exercise training. These findings add to a growing body of research aimed at explaining inter-individual variability in exercise intervention outcomes and may contribute to individualizing the exercise prescription. Part 2 of this thesis used a cross-sectional approach and investigated firstly whether there was evidence for metabolic adaptation to weight loss/regain in response to long term weight maintenance, potentially predisposing individuals to future weight gain/regain. Secondly, I investigated whether insulin sensitivity is altered as a result of prior weight loss history, or whether successful weight loss restores insulin sensitivity to levels that are comparable to phenotypically similar controls with no weight loss history. Weight stable, BMI-matched South African women aged 20-45 years with or without a history of prior weight loss were screened and recruited. Four groups were defined as follows: Weight Reduced (RED, n=15) - lost at least 15% of body weight & maintained a reduced weight (BMI ≤ 27kg.m-2 ) for over 12 months (15% of body weight), but relapsed back to overweight or obese (BMI ≤ 27kg.m-2 ); and overweight or obese (BMI ≤ 27kg.m-2 ) stable-weight controls (OSW, n=11) - no history of significant weight loss. The first study in Part 2 (Chapter 4) compared metabolic rate and substrate utilization in RED and REL to their respective BMI-matched controls with no weight loss history, both at rest and in response to a high fat meal challenge. Metabolic rate and substrate utilization were measured both at rest, immediately after consumption of the high fat test-meal and every hour thereafter for three hours. Dietary intake (3 x 24h recalls) and physical activity (ACTi Graph GT3X accelerometer worn for 7 days) data was collected and body composition was measured (bioelectrical impedance, BIA). Questionnaires were also completed covering weight history, socio-economic status and eating behaviour. Results showed that there was no difference in either resting EE or substrate utilization between the RED and REL compared to the respective BMI-matched controls, after accounting for fat free mass (FFM). The TEF, postprandial EE (absolute and per kg FFM), post-prandial energy balance, RER, fat oxidation rate and post-prandial fat balance were similar between RED and REL compared to their respective controls, indicating that there was no evidence of metabolic adaption to weight loss. However, successful weight-loss maintainers did show behavioural strategies that may have counteracted weight-loss associated adaptive thermogenesis and supported weight-loss maintenance. These individuals had manipulated macronutrient intake (increasing protein and reducing carbohydrate intake), were more physically active, exhibiting less sedentary behaviour and increased moderate and vigorous activity, and had greater fat free soft tissue mass (FFSTM). While the presence of adaptive thermogenesis is not disputed in these results, the distinct physiological and behavioural differences together observed in the RED may have been instrumental in attenuating weight-loss associated declines in EE, shown to persist into weight-loss maintenance. Together with these lifestyle strategies, weight reduced individuals also reported greater dietary restraint in comparison to controls. This is surprising after such a significant period of weight-loss maintenance (median weight-loss maintenance: 30 months) and highlights the ongoing challenges to maintain reduced weight. These findings contribute to the relatively smaller body of research into the longer-term persistence of weight-loss associated adaptive responses in comparison to that covering the acute weight loss phase. It also highlights strategies that may be effective in counteracting metabolic adaption to weight loss. As such, these strategies may warrant inclusion as part of weight-loss maintenance programs as they potentially help to reduce the risk for weight regain as a result of weight-loss associated adaptive thermogenesis. The next study in Part 2 of the thesis (Chapter 5) aimed to examine the impact of successfully maintained weight loss and weight-loss relapse on insulin sensitivity compared to BMImatched controls without a weight loss history. Predictors of variability in insulin sensitivity were also explored. Following the measurement of resting metabolic rate and substrate utilization a 75g oral glucose tolerance test was used to determine fasting and 2hr plasma glucose and insulin. The Homeostatic Model Assessment (HOMA-IR) and insulin sensitivity index (ISI(0,120)) were used to assess insulin sensitivity. A novel finding of this study was that successfully maintained, weight-reduced individuals displayed enhanced measures of insulin sensitivity (lower HOMA-IR and higher ISI(0,120) measurements), compared to all other groups, including BMI-matched controls with no weight loss history. Previously studies have investigated changes in insulin sensitivity in response to weight loss and in weight-loss maintenance, but not necessarily in comparison to individuals without a weight loss history as defined by this study protocol. With weight regain however, insulin sensitivity measures for REL were not different compared to either LSW or OSW, showing that enhanced insulin sensitivity accompanying weight loss is likely reversed with weight regain. Prior weight history, fasting substrate utilization, measures of body weight and composition, protein intake per kilogram, physical activity and CRF were all associated with measures of insulin sensitivity. Using these variables in regression models, ≈60% of the variability in insulin sensitivity in both HOMA-IR and ISI(0,120). Weight loss and weight regain history followed by fasting RER were the most significant independent predictors of insulin sensitivity. In conclusion, a novel finding was that successfully weight-reduced individuals are more insulin sensitive than their BMI-matched controls with no weight loss history, independent of dietary intake and physical activity. This remains evident even after significant periods of maintaining the reduced weight. Weight loss maintenance programs are essential to retaining metabolic benefits acquired through weight loss. Remaining physically active by reducing sedentary behaviour and in particular including small amounts of vigorous physical activity significantly predicts improved insulin sensitivity. This thesis includes a number of novel findings. In Part 1, we showed that in response to exercise training gynoid FM, rather than VAT, was reduced in sedentary obese black SA women undergoing a 12 week exercise intervention, which may represent an important ethnic/gender specific response. We also showed that substrate utilization plays an important role in altering body composition and CRF in response to an exercise intervention. Greater fat oxidative capacity at the outset resulted in an enhanced ability to reduce gynoid FM in response to exercise training. Furthermore, a greater reliance on carbohydrate rather than fat oxidation during baseline testing predicted a poorer CRF response. Identification of individuals with a lower capacity for fat oxidation at the outset of an exercise intervention may therefore allow for a more targeted exercise prescription, which may in turn improve outcomes of exercise interventions. The lack of clinically significant weight loss suggests that future exercise interventions should prescribe exercise EE of sufficient magnitude to achieve weight loss and emphasize adherence to this prescription or include some dietary restriction. Education around the possible adaptive responses to increased EE and the imposed energy deficit, highlighting the strategies employed by weight reduced individuals from Part 2 of this thesis, may help to attenuate potential metabolic adaption to increased EE and further improve the weight loss outcomes of exercise-only interventions. It may also help to inform weight-loss maintenance programs to assist individuals to maintain the reduced weight following weight loss. The enhanced insulin sensitivity in weight reduced individuals as shown in Part 2, may potentially represent an ongoing and persistent adaptive response to weight loss that may in itself increase the risk for weight-loss relapse. Education around the physiological adaption to significant weight loss and emphasizing strategies that may counteract this metabolic adaptation may improve the efficacy of both weight-loss and weight-loss maintenance programs.