Department of Physiological Sciences

Permanent URI for this community

https://scholar.sun.ac.za/handle/10019.1/232

Browse

Now showing 1 - 20 of 278

Acute simulated hypoxia and ischemia in cultured C2C12 myotubes : decreased phosphatidylinositol 3-kinase (PI3K)/Akt activity and its consequences for cell survival
(Stellenbosch : Stellenbosch University, 2008-12) Thomas, Mark Peter; Engelbrecht, Anna-Mart; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
Cells are equipped with an array of adaptive mechanisms to contest the undesirable effects of ischemia and the associated hypoxia. Indeed, many studies have suggested that there is an increase in the PI3K/Akt pathway activation during hypoxia and ischemia. Damaged muscle can be regenerated by recruiting myogenic satellite cells which undergo differentiation and ultimately lead to the regeneration of myofibres. The C2C12 murine myogenic cell line is popular for studying myogenesis in vitro, and has been used in many studies of ischemic microenvironments. PI3K/Akt pathway activity is increased during C2C12 myogenesis and this is known to produce an apoptosis resistant phenotype. In this study, we provide evidence that high basal levels of PI3K activity exist in C2C12 myotubes on day ten post-differentiation. Ischemia is characterized by depleted oxygen and other vital nutrients, and ischemic cell death is believed to be associated with an increasingly harsh environment where pH levels decrease and potassium levels increase. By employing a model that mimics these changes in skeletal muscle culture, we show that both acute simulated ischemia and acute hypoxia cause decreases in endogenous levels of the p85 and p110 subunits of PI3K and a consequent reduction in PI3K activity. Supplementing skeletal muscle cultures with inhibitors of the PI3K pathway provides evidence that the protective effect of PI3K/Akt is subsequently lost in these conditions. Using Western blot analysis, a PI3K ELISA assay as well as known inhibitors of the PI3K pathway in conjunction with the MTT assay we are able to demonstrate that the activation of downstream effectors of PI3K, including Akt, are concurrently decreased during acute simulated ischemia and acute hypoxia in a manner that is independent of PDK-1 and PTEN and that the decreases in the PI3K/Akt pathway activity produce a knock-on effect to the downstream signalling of transcription factors, such as Fox01 and Fox04, in our model. We proceed to provide compelling evidence that the apoptotic resistance of C2C12s is at least partially lost due to these decreases in PI3K/Akt pathway activity, by showing increased caspase-3 and PARP cleavage. Then, using vital staining techniques and a DNA fragmentation assay, we demonstrate increased cell membrane impairment, cell death and apoptosis after three hours of simulated ischemia and hypoxia in cultured C2C12 myotubes. In addition to the main findings, we produce evidence of decreased flux through the mTOR pathway, by showing decreased Akt-dependant phosphorylation at the level of TSC2 and mTOR during simulated ischemia and hypoxia. Finally, we present preliminary findings indicating increased levels of HIF1α and REDD-1, representing a possible oxygen sensing mechanism in our model. Therefore, we show that there is in fact a rapid decrease in PI3K/Akt activity during severe, acute simulated ischemia and hypoxia in C2C12 myotubes on day ten post-differentiation, and this causes a concomitant down regulation in cell survival pathways and increased activity of cell death machinery. Thereafter, we propose a possible mechanism of action and provide a platform for future studies.
Ageing-associated oxidative stress and inflammation are alleviated by products from grapes
(Hindawi, 2016) Petersen, K. S.; Smith, Carine
Advanced age is associated with increased incidence of a variety of chronic disease states which share oxidative stress and inflammation as causative role players. Furthermore, data point to a role for both cumulative oxidative stress and low grade inflammation in the normal ageing process, independently of disease. Therefore, arguably the best route with which to address premature ageing, aswell as age-associated diseases such as diabetes, cardiovascular disease, and dementia, is preventative medicine aimed at modulation of these two responses, which are intricately interlinked. In this review, we provide a detailed account of the literature on the communication of these systems in the context of ageing, but with inclusion of relevant data obtained in other models. In doing so, we attempted to more clearly elucidate or identify the most probable cellular or molecular targets for preventative intervention. In addition, given the absence of a clear pharmaceutical solution in this context, together with the everincreasing consumer bias for natural medicine, we provide an overview of the literature on grape (Vitis vinifera) derived products, for which beneficial effects are consistently reported in the context of both oxidative stress and inflammation.
An alternative approach to premature luteal regression
(Stellenbosch : Stellenbosch University, 2006-12) Pretorius, Willem S.; Barry, Daniel Malan; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Premature luteal regression occurs on average in 30% of superovulated sheep ewes. This phenomenon occurs early in the cycle before the embryo’s can be collected and is a major contributor to failure in embryo transfer programs. This research was done to understand the physiological mechanisms involved. Chapter two provides a general background of the physiology of natural luteolysis and the maternal recognition of pregnancy. The chapter introduces some new concepts on the topic of cell death and provides a recent literature review on research done on the phenomenon of premature luteal regression. This chapter forms the base of ideas and arguments that follows in the two studies containing new original work in this field. The research contained in this thesis comprises of two in vivo studies. The first study (Chapter 3) compare premature luteal regression to Prostaglandin F2α (PGF2α) induced regression with emphasis on the changes in levels of the steroid hormones progesterone (P4) and estradiol - 17β (E2-17β) and changes in structure and ultra structure. The following conclusions were made: 1. Premature luteal regression is not merely inadequate luteal support, but indeed early luteal regression, since seasonal influences could merely be nutritional influences, and a definitive increase in P4 were recorded in animals exhibiting the phenomena. 2. Nutritional influences could play a role, but the type and quality of nutrients and mechanism involved, is still unclear. 3. PGF2α-induced regression differs from premature luteal regression in that: a) The progression of functional and structural regression in PGF2α -induced regression is slower than in premature luteal regression. b) Regressed corpora lutea do not occur with normal functioning corpora lutea. 4. There is a distinct second E2-17β peak preceding the decline in P4 in animals that exhibits signs of premature luteal regression. A threshold initiating premature luteal regression was not established. The second study (Chapter 4) compares the changes in the ovine β estradiol - 17 β receptor (oERβ) between premature luteal regression and PGF2α induced regression. The study concludes that there could be a potential role for oERβ in premature luteal regression. The findings of these two studies raise some questions about the conventional perception that early release of PGF2α is the cause of premature luteal regression. The thesis concludes in a hypothesis (Chapter 4) explaining the phenomenon.
Amino acid starvation sensitizes resistant breast cancer to doxorubicin-induced cell death
(Frontiers Media, 2020) Thomas, Mark; Davis, Tanja Andrea; Nell, Theo; Sishi, Balindiwe J. N. (Jennifer Nonkosazana); Engelbrecht, Anna-Mart
Many clinical trials are beginning to assess the effectiveness of compounds known to regulate autophagy in patients receiving anti-cancer chemotherapy. However, autophagy inhibition, through exogenous inhibitors, or activation, through starvation, has revealed conflicting roles in cancer management and chemotherapeutic outcome. This study aimed to assess the effect of amino acid starvation on doxorubicin-treated breast cancer cells by assessing the roles of autophagy and apoptosis. An in vitro breast cancer model consisting of the normal breast epithelial MCF12A and the metastatic breast cancer MDAMB231 cells was used. Apoptotic and autophagic parameters were assessed following doxorubicin treatments, alone or in combination with bafilomycin, ATG5 siRNA or amino acid starvation. Inhibition of autophagy, through ATG5 siRNA or bafilomycin treatment, increased caspase activity and intracellular doxorubicin concentrations in MCF12A and MDAMB231 cells during doxorubicin treatment. While amino acid starvation increased autophagic activity and decreased caspase activity and intracellular doxorubicin concentrations in MCF12A cells, no changes in autophagic parameters or caspase activity were observed in MDAMB231 cells. Our in vivo data showed that 24 h protein starvation during high dose doxorubicin treatment resulted in increased survival of tumor-bearing GFP-LC3 mice. Results from this study suggest that short term starvation during doxorubicin chemotherapy may be a realistic avenue for adjuvant therapy, especially with regards to the protection of non-cancerous cells. More research is however, needed to fully understand the regulation of autophagic flux during starvation.
Anthracycline-induced cardiotoxicity : the role of proteolytic pathways
(Stellenbosch : Stellenbosch University, 2012-03) Sishi, Balindiwe J. N. (Balindiwe Jennifer Nonkosazana); Engelbrecht, Anna-Mart; Loos, Benjamin; Van Rooyen, Jacques; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Introduction: The anthracyclines (ACs), daunorubicin (DNR) and doxorubicin (DXR) are two of the most effective drugs known for the treatment of systemic neoplasms and solid tumours. However, their clinical use is often hampered by their dosedependent cumulative cardiotoxicity, which leads to irreversible and fatal druginduced congestive heart failure. The mechanism by which ACs induces heart damage is not fully understood. Recent reports have indicated that DXR activates autophagy and ubiquitin proteasome-mediated degradation of specific transcription factors, however, no reports exists on the effect of ACs on the E3 ubiquitin ligases, MuRF-1 and MAFbx. The aim of the first part of the study was therefore to investigate the effect of DNR treatment on the protein and organelle degradation systems in the heart and to elucidate the signalling mechanisms involved. Although this model was ideal in allowing the investigation of the signalling pathways which are affected by DNR, it did not allow for further exploration or manipulation of signalling pathways that may be of potential benefit in this context. The in vitro model was therefore used to validate the hypothesis that increased autophagy alleviates AC-induced cardiotoxicity and delays the onset of cardiomyocyte death. The aims for the second part of the study were (i) to characterize the effect of DXR in H9C2 cells, (ii) to determine whether the induction/inhibition of autophagy in combination with DXR alleviates cytotoxicity and (iii) to investigate the influence of increased/decreased autophagy in combination with DXR on reactive oxygen species (ROS) production, mitochondrial function, endoplasmic reticulum (ER) stress and the ubiquitin proteasome pathway. In the final part of this study, an in vivo model was used to assess the potential benefit of autophagy in a novel GFP-LC-3 tumour bearing mouse model of acute DXR-induced cardiotoxicity. Material and Methods: Adult rats were divided into two groups where one group received six intraperitoneal injections of 2 mg/kg DNR on alternate days and the other group received saline injections as control. Hearts were excised and perfused on a working heart system the day after the last injection and freeze clamped for biochemical analysis. H9C2s were cultured and treated with Bafilomycin A1 (10 nM, inhibitor of autophagy) for 6 hrs, Rapamycin (50 μM, inducer of autophagy) for 24 hrs, DXR (3 μM) for 24 hrs or a combination of these drugs. Following treatment, cells were harvested and assessed for cell death, proteolytic activity and oxidative stress using western blotting, fluorescence microscopy and flow cytometry. In the final phase of the study, twenty-four female mice were injected at 8 weeks with a mouse breast cancer cell line (EO771) and after observation of tumour growth, animals were either treated with one injection (i.p.) of Rapamycin (4 mg/kg), two injections (i.p.) of DXR (10 mg/kg) or a combination of the two drugs. After the experimental protocol, mice were terminated and their hearts were rapidly excised. The hearts were divided cross-sectionally and utilized for biochemical and histological analyses. Results and Discussion: DNR treatment significantly attenuated myocardial function and increased apoptosis in the ex vivo heart model. DNR-induced cardiac cytotoxicity was associated with the upregulation of two E3 ubiquitin ligases, MuRF-1 and MAFbx as well as a significant increase in two markers of autophagy, beclin-1 and LC-3. These changes observed in the heart were also associated with attenuation of the PI3-kinase/Akt signalling pathway. The augmentation of autophagy with rapamycin before DXR treatment significantly reduced cell death in the in vitro model. Indeed, rapamycin treatment demonstrated to be a vital survival mechanism for acute DXR-induced cardiotoxicity as it decreased cellular ROS production, improved mitochondrial function and prevented nuclear translocation of DXR. Moreover, these changes in cardiomyocytes were also associated with a reduction in the ubiquitin-proteasome pathway (UPP). In the final part of this study, a novel tumour bearing GFP-LC3 mouse model was developed to confirm the results obtained in the in vitro study. It was demonstrated that acute DXR-induced cardiotoxicity resulted in increased apoptosis, the inhibition of autophagy and increased proteolysis via the UPP. These findings were associated with a reduction in body weight and cardiomyocyte cross-sectional area. The cardiotoxic effects of DXR were substantially reduced when autophagy was induced with rapamycin. Taken together, our data strongly indicates that it is possible to attenuate the cardiotoxic effects of doxorubicin in cancer patients by carefully controlling the levels of autophagy using rapamycin as adjuvant therapy.
Anthropometric characteristics and changes with HIV and ART in a randomly selected population in the Drakenstein region Western Cape Province
(Stellenbosch : Stellenbosch University, 2014-12) Beukes, Dillan Charles; Nell, Theo A.; Essop, M. Faadiel; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Background - Highly active antiretroviral therapy (HAART) has extended life expectancy and enhanced the well-being of HIVpositive individuals. Since there are concerns regarding HAART-mediated onset of cardio-metabolic diseases in the long-term, we evaluated the anthropometric profile of HIV-infected individuals in the Drakenstein District (Western Cape, South Africa). - Objective of study - The primary objective of this study was to document the anthropometric characteristics within and HIV infected population in the Drakenstein region of the Western Cape Province of South Africa. - Methods - HIV-positive patients (n=44 males, n=102 females; 20-40 yrs.) were recruited for three groups: 1) control (HIVnaïve), 2) HIV-positive (HAART ≤ 0-36 months), and 3) HIV-positive (HAART ≥ 36 months). Participants underwent a) anthropometric (triceps skin fold [TSF], and b) bioelectrical impedance measurements (body cell mass [BCM], fat free mass [FFM], protein, muscle mass (MM), mineral, total body potassium (TBK) and calcium (TBCa), glycogen, and fat mass [FM]). - Results - Our data reveal that HIV-positive males on HAART ≤ 0-36 months displayed a trend for lower body cell mass (BCM), fat free mass (FFM), fat mass (FM), triceps skinfold (TSF) and protein content (vs. control). Females exhibited reduced BCM (p=0.001) and lower protein (p=0.003), muscle mass (p=0.001), glycogen (p=0.001), FM (p=0.0005) and FFM (p=0.002) content. However, with longer-term treatment (HAART ≥ 36 months), females displayed higher BCM (p=0.0001), protein (p=0.01), muscle mass (p=0.0003), glycogen (p=0.0001), FM (p=0.00003) and FFM (p=0.0002) vs. the 0-36 months treatment group. Their waist-to-hip ratio also increased vs. the naïve female group (p=0.02). By contrast, males on HAART ≥ 36 months did not show any significant increases vs. the HAART ≤ 0-36 month’s group. - Conclusions - This study demonstrates observed striking gender-based anthropometric differences in South African HIVpositive individuals on HAART. While both genders initially exhibit muscle wasting, HIV-positive females show a strong improvement with longer-term treatment vs. males. However, higher abdominal fat accumulation in females with longer-term treatment potentially increases their risk for the future onset of cardio-metabolic complications.
Anti-inflammatory cellular targets on neutrophils elucidated using a novel cell migration model and confocal microscopy : a clinical supplementation study
(BioMed Central, 2018-01-05) Smith, T.; Engelbrecht, L.; Smith, C.
Background In vivo studies have shown grape seed-derived polyphenols (GSP) to benefit in recovery from muscle injury by modulation of neutrophil infiltration into damaged tissue, thereby reducing secondary damage, as well as by facilitating an early anti-inflammatory macrophage phenotype shift. The current study aimed to provide data in this context from human models and to elucidate specific molecular targets of GSP. Using a placebo-controlled, double-blind study design, eighteen normally healthy volunteers between the ages of 18–35 years old (13 female and 5 male) were orally supplemented with 140 mg/day of GSP for 2 weeks. Blood samples (days 0 and 14) were comprehensively analysed for in vitro neutrophil chemokinetic capacity towards a chemotaxin (fMLP) using a novel neutrophil migration assay, in combination with live cell tracking, as well as immunostaining for neutrophil polarisation factors (ROCK, PI3K) at migration endpoint. Macrophage phenotype marker expression was assessed using flow cytometry. Results fMLP induced significant chemokinesis (P < 0.01), validating our model. GSP did not exert a significant effect on neutrophil chemokinesis in this non-compromised population, but tended to decrease overall ROCK expression in fMLP-stimulated neutrophils (P = 0.06). Macrophage phenotype markers CD274 and MPO – indicators of a pro-inflammatory M1 phenotype – seemed to be normalised relative to baseline expression levels after GSP treatment. Conclusions Current data suggest that GSP may have a modulatory effect on the ROCK-PI3K-PTEN system, but results in this normal population is not conclusive and should be confirmed in a larger, more inflamed population. Potential modulation of macrophage phenotype by GSP should be investigated further.
Antioxidant (Oxiprovin TM) supplementation and muscle recovery from contusion injury - an in vivo study
(Stellenbosch : Stellenbosch University, 2007-12) Kruger, Maria Jacoba; Smith, Carine; Smith, R. M.; Myburgh, Kathryn H.; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Human studies on the response of muscle to contusion injury are limited, probably due to the large variability in injury severity and the non-specificity of clinical symptoms reported. To circumvent this problem, several experimental animal models have been designed to study muscle damage and regeneration after contusion injuries. However, the majority of techniques currently used to induce contusion injury are very invasive and therefore not optimal. Furthermore, published studies regarding clinical treatment of such injuries are limited. The main aims of this study were therefore: a) to establish and characterise an in vivo model of non-invasive contusion injury, and b) to assess the effect of pre-injury chronic administration of the antioxidant supplement Oxiprovin™ - a natural grape seed extract (GSE) - on skeletal muscle recovery after experimentallyinduced injury. Two groups of male Wistar rats were subjected to 14 days of oral administration of isovolaemic placebo (sterile isotonic saline) or GSE (20 mg/kg/day) prior to induced contusion. Contusion injury was induced with the mass-drop technique, and recovery parameters assessed for up to 14 days post-injury. Placebotreated rats on average exhibited a 56 % higher creatine kinase (CK) activity when compared to the GSE-treated rats when area under the curve (AUC) was calculated for 14 days post-injury (p < 0.001). In the placebo group, plasma oxygen radical absorbance capacity (ORAC) was unchanged over time, but muscle ORAC was significantly increased by day 7 post-injury (p < 0.001). In the GSE group, a significant decrease in both plasma (p < 0.01) and muscle ORAC (p < 0.001) was evident 4 hr after injury, followed by a significant increase by day 3 (p < 0.05 and p < 0.001 respectively). CD34+ satellite cell (SC) numbers (quiescent and activated) peaked earlier in GSE-treated rats when compared to placebo-treated rats (4 hours vs. day 7 post-injury). Total satellite cell number (CD56+) also peaked earlier in GSE-treated rats than in placebo-treated rats (4 hours vs. 3 days post-injury), while M-cadherin+ SC numbers (quiescent, activated or proliferating) in both treatment groups were significantly increased 4 hours post-injury (p < 0.001), but more so in the placebo group. In GSE-treated rats when compared to placebo-treated rats, newly generated muscle fibres (displaying central nuclei and MHCf +) both appeared (day 3 vs. day 7 post-injury) and peaked in number (day 3 vs. day 7 post-injury; increase from baseline p < 0.001 for both) earlier. The results of this study demonstrate that we have successfully established an in vivo model for non-invasive contusion injury in rats. Furthermore, we have shown that Oxiprovin™: a) increased the ability to scavenge reactive species generated after injury and b) resulted in the activation of satellite cells and formation of newly generated muscle fibres at an earlier time point, thus accelerating the recovery of skeletal muscle after a standardised contusion injury.
Anxiety : an overlooked confounder in the characterisation of chronic stress-related conditions?
(Public Library of Science, 2020-04-16) Viljoen, Monet; Benecke, Rohan M.; Martin, Lindi; Adams, Rozanne C. M.; Seedat, Soraya; Smith, Carine
Although anxiety disorders are among the most prevalent of psychiatric disorders, childhood trauma-related studies seldom consider anxiety proneness as distinct aetiological contributor. We aimed to distinguish between trauma- and anxiety-associated physiological profiles. South African adolescent volunteers were categorised for trauma exposure (CTQ, mean score 39±11) and anxiety proneness (AP)(CASI, mean score 37±7, STAI-T, mean score 41±8). Circulating hormone and leukocyte glucocorticoid receptor levels, as well as leukocyte functional capacity, were assessed. AP was associated with lower DHEAs (P<0.05) and higher leukocyte GR expression (P<0.05). DHEAs was also negatively correlated with anxiety sensitivity (CASI, P<0.05). In conclusion, AP may have more predictive power than trauma in terms of health profile. Increased glucocorticoid sensitivity previously reported after trauma, may be a unique function of anxiety and not trauma exposure per se. DHEAs concentration was identified as potentially useful marker for monitoring progressive changes in HPA-axis sensitivity and correlated with psychological measures of anxiety.
Are early proteomic and metabolic changes induced by long-term sugar-sweetened beverage consumption the key to unlocking the cardio-metabolic pandemic?
(Stellenbosch : Stellenbosch University, 2017-03) Benade, Janina; Essop, M. Faadiel; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: INTRODUCTION: Cardio-metabolic diseases (e.g. type 2 diabetes mellitus) are a major cause of mortality worldwide. The incidence of cardio-metabolic diseases continues to increase, especially in low and middle income countries. This “pandemic” is possibly brought about by a fairly universal shift towards a more “Westernized” diet. High sugar consumption - a hallmark of the “Westernized” diet - may play a key role in the onset of cardio-metabolic diseases. Accordingly, our research focus moved towards sugar-sweetened beverages (SSBs) as it is a major source of added dietary sugars. The current study aimed to elucidate underlying mechanisms leading to the development of cardiometabolic diseases by exploiting a novel rat model of long-term SSB intake, and by focusing on the liver as a major metabolic organ. Here we evaluated well-known systemic markers together with hepatic proteome analysis and downstream consequences. METHODS: Male Wistar rats ( 200 g) were gavaged with 3-5.1 mL SSB daily for three and six months, respectively. The two control groups were gavaged with an iso-volumetric amount of water and iso-caloric amount of butter, respectively. Body weight and systemic blood markers were measured. A proteomic expression analysis was performed on the six-month liver samples. The rest of our experimental work was guided by the proteomic results. Four markers for oxidative stress were evaluated: malondialdehyde, conjugated dienes, reduced:oxidized glutathioneand oxygen radical absorbance capacity. The non-oxidative glucose pathways (NOGPs): polyol pathway, hexosamine biosynthetic pathway, advanced glycation end-products formation and protein kinase C activation; were measured as elevated activity could be indicative of impaired glycolytic flux. The liver histology was investigated with Hematoxylin and Eosin and Masson’s Trichrome stains, respectively. Finally, Western blotting techniques were used to evaluate markers of inflammation. RESULTS: SSB consumption had little effect on systemic markers of cardio-metabolic health. Our proteomic analysis revealed that the expression level of 140 proteins was significantly altered in the SSB group, with a major finding that SSB consumption induces hepatic endoplasmic reticulum (ER) stress. Initially the liver adapted to SSB-mediated nutrient overload by increasing oxidative phosphorylation, suppressing protein transcription, degrading misfolded proteins and improving protein folding capacity. However, due to prolonged stress liver cells entered an ‘’alarm phase’’ marked by a decrease in mitocholdrial metabolism. The proteomic results further revealed that SSB-induced effects are largely attributed to excess caloric intake versus SSBs per se. Surprisingly, oxidative stress did not precede ER stress as there were no significant changes in any of the oxidative stress markers here evaluated. The activity of the NOGPs did not increase significantly thus suggesting that moderate SSB intake did not suppress glucose metabolism and the glycolytic pathway in particular. Conversely, SSB intake increased hepatic lipid storage while limited changes were detected between the groups regarding inflammation and stress signaling. CONCLUSION: Frequent SSB consumption triggers metabolic changes in the liver, i.e. ER stress despite the lack of obvious manifestation of macroscopic “warning signs”. Thus the current study identifies hepatic ER stress as a relatively early result of long-term SSB consumption and it therefore emerges as a unique therapeutic target.
ART-related body composition changes in adult women in a semi-rural South African context
(Stellenbosch : Stellenbosch University, 2006-12) De Bruto, Petro C.; Myburgh, Kathryn H.; Smith, Carine; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: The aim of this study was to investigate practical methods of monitoring AIDS related wasting and lipodystrophy in a resource-poor clinical setting with HIV infected women as the population group of interest. Measurement of body composition changes using anthropometry is both cost- and time-efficient. Various different skinfolds were taken and two different equations (the equations of Pollock et al. (1975) and Durnin and Womersley (1974) for calculating body fat were used to determine the most promising method or methods of monitoring body composition changes in a clinical setting. Detailed anthropometric measurements were performed, as well as selected measurements for haematological parameters and quality of life (QoL) for a group of 8 participants on antiretroviral medication (ART group) and 6 participants who were not on treatment (TN group). New variables namely, intra-abdominal indicator (IAI) and a percent of ideal body mass to percent of ideal arm circumference ratio (%IBW:%IAC) were investigated as possible indicators of lipodystrophy. Although measurements were taken at various timepoints, three specific time-points were chosen for data-analysis for the ART group and two time points for the TN group. These three time-points were, baseline (on the day of recruitment for TN participants and within one month before the initiation of treatment for ART participants), short-term (2 to 12 weeks after treatment initiation or the baseline measurement or for the ART and the TN participants) and long-term (within one and a half year of treatment initiation for the ART group). ART and TN participants did not differ for many variables at baseline. The major differences between ART and TN were in measured and derived variables of the arm, especially percent of ideal arm circumference (%IAC) and upper arm fat area (UAFA), which were significantly lower in the ART group. CD4+ and QoL improved significantly for the ART participants from baseline to long-term. This was not associated with changes in muscle mass, but rather some fat mass variables. Participants on antiretroviral medication exhibited changes relating to abdominal obesity. It was concluded that antiretroviral therapy contributed greatly to the QoL of the participants and it probably aided in the recovery from wasting for at least one participant in this study. Measures of the arm can be used in a rural clinical setting to effectively monitor patients with regard to AIDS related wasting. The new variables IAI and %IBW:%IAC could be helpful in the monitoring of lipodystrophy and should be investigated in future research.
Aspalathin protects the heart against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression
(MDPI, 2017) Dludla, Phiwayinkosi V.; Muller, Christo J. F.; Joubert, Elizabeth; Louw, Johan; Essop, M. Faadiel; Gabuza, Kwazi B.; Ghoor, Samira; Huisamen, Barbara; Johnson, Rabia
Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress, and apoptosis. The protective mechanism of ASP remains unknown. However, as one of possible, it is well known that phytochemical flavonoids reduce oxidative stress via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation resulting in up-regulation of antioxidant genes and enzymes. Therefore, we hypothesized that ASP protects the myocardium against HG- and hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice, respectively. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for six weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for six weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced oxidative stress through activation of Nrf2 and its downstream target genes.
Assessment of endocrine stress status in athletes – new twists to the tale
(Health and Medical Publishing Group, 2005) Smith, C.; Myburgh, Kathryn H.
Objective. Cortisol concentration at rest seems to be an insensitive marker for endocrine stress status in athletes. Therefore, the aim of this review was to identify potentially more sensitive parameters which could be used to monitor endocrine stress status during chronic exercise training. In order to gain more insight from studies not directly related to exercise science, this review also includes findings from studies investigating responses to psychological stress in healthy individuals and in patients suffering from chronic disease. Data sources. Medline. Study selection and data extraction. Key words (e.g. exercise stress, psychological stress, overtraining, chronic fatigue, dehydroepiandrosterone (DHEA), chronic inflammation). Only studies published in peer-reviewed journals included in the International Science Index were used. Care was specifically taken not to over-represent any particular research group’s articles. Data synthesis. A qualitative synthesis was done, based on all papers included in the review. Conclusions. Four main conclusions were drawn: (i) instead of considering changes in mean cortisol concentration over time for a group of athletes, high- and low-responders should be identified at baseline and their responses considered separately; (ii) it may be more useful to express cortisol concentration as a ratio to either testosterone or DHEA-sulphate (DHEAs) concentration than assessing either the catabolic or anti-catabolic variable on its own; (iii) in response to stress, cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG) do not seem to play major roles in the regulation of circulating concentrations of bioactive cortisol and testosterone respectively; and (iv) it is crucial to allow sufficient recovery from the most recent exercise session to ensure that proper resting blood samples are obtained for assessment of chronic effects of training on endocrine status.
An assessment of ischemia-reperfusion injury in rats exposed to chronic psychological stress
(Stellenbosch : Stellenbosch University, 2019-12) Oliver, Lukas Van Zyl; Essop, M. Faadiel; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Cardiovascular disease remains the leading cause of death worldwide. Apart from known risk factors such as poor dietary intake, physical inactivity and smoking, chronic psychological stress is emerging as an important modifiable risk factor in the development of cardiovascular disease. The body relies on two physiological mechanisms to counter acute stressors and to achieve and/or maintain homeostasis, i.e. the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. However, chronic activation of these systems can lead to the disruption of cellular and systemic processes that could potentially result in the development of neurological or psychosomatic diseases. Both chronic stress and ischemia-reperfusion injury are associated with a robust inflammatory response and the induction of oxidative stress. Does chronic psychological stress render the heart more susceptible to ischemia and reperfusion damage, and what are the role(s) of oxidative stress and inflammation in stress-related cardiac dysfunction? These questions will form the basis of this review. Following a comprehensive review, we established that chronic stress does render the heart more susceptible to damage following ischemia-reperfusion. After reviewing the mechanisms involved in both ischemia-reperfusion and chronic stress, we hypothesized that chronic stress induced inflammation and oxidative stress are major contributors in aggravated ischemia-reperfusion injury.
Assessment of Metabolic Therapy for Acute Heart Failure
(Stellenbosch : Stellenbosch University, 2017-03) Kimar, Charlene Patricia; Essop, M. Faadiel; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Introduction Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart disease cases in Africa. Increased fatty acid oxidation (FAO) with heart failure (HF) triggers detrimental effects on the myocardium, we hypothesized that diabetic rat hearts subjected to AHF display lower cardiac function vs. controls and that Trimetazidine (TMZ) (a partial FAO inhibitor) counters this effect. Aims 1)To establish an ex vivo AHF model for diabetic hearts; 2) Assess whether TMZ treatmentoffers cardioprotection to diabetic rat hearts subjected to an AHF protocol; and 3) Delineate underlying mechanisms by evaluating markers for oxidative stress, mitochondrial uncoupling, apoptosis and metabolic dysregulation. Methods Vehicle control male Wistar rats were injected with citrate buffer. To induce diabetes rats were administered streptozotocin (60 mg/kg) for one week vs. non-diabetic controls. Hearts were perfused on the Langendorff retrograde perfusion system for three phases: Stabilization - (11 mM glucose- non-diabetic, and 30 mM glucose- diabetic hearts) at 100 cm H2O (30 min); AHF – (1.5 mM palmitic acid, 2.5 mM glucose) at 20 cm H2O (35 min); and Recovery– (1.5 mM palmitic acid, 11 mM glucose or 30 mM glucose) at 100 cm H2O (30 min). 1 μM TMZ was administered at the start of recovery. In addition, we evaluated necrosis and infarct size by tetrazolium (TTC) staining at the end of the AHF phase. Western blotting was performed for markers of apoptosis (pBAD/BAD), oxidative stress (superoxide dismutase 2 [SOD2], conjugated dienes [CDs], thiobarbituric acid reactive substances (TBARS), reduced/oxidized glutathione [GSH/GSSG] analysis, oxygen radical absorbance capacity [ORAC]), mitochondrial uncoupling (uncoupling protein 2 [UCP2]) and metabolic dysregulation (advanced glycation end product [AGE] and polyol pathway analyses). We investigated direct effects of TMZ (1 μM) in H9c2 cardiomyoblasts exposed to 500 μM palmitate for 21 hours and assessed the effects of TMZ treatment on fatty acid-induced oxidative stress and apoptosis. Results Reduced function was seen for all groups in recovery vs. controls, while AHF-diabetic showed worse outcomes vs. AHF alone. TMZ treatment resulted in a robust increase in left ventricular developed pressure (LVDP) for diabetic hearts vs. controls. Infarct size assessment showed no differences. TMZ treated diabetic hearts also displayed lower AGE and higher polyol pathway activation vs. respective controls. However, several markers of the AGE pathway did not show any significant differences for any groups. Non-diabetic and diabetic hearts displayed increased oxidative stress (TBARS) compared to their counterparts. TMZ treatment resulted in anti-apoptotic effects in hearts subjected to AHF. TMZ exhibited antioxidant effects by lowering fatty acid-induced mitochondrial oxidative stress in cells. Conclusion This study successfully established a novel ex vivo model of AHF for the diabetic rat heart, and TMZ treatment resulted in cardioprotection for diabetic hearts. Our data suggest that TMZ may mediate some of its cardioprotective effects by acting as an anti-oxidant to lower myocardial oxidative stress triggered during AHF. The findings also indicate that TMZ treatment may lower the formation of damaging AGEs in the diabetic heart. TMZ therefore, emerges as a putative therapeutic target to be considered as sole and/or combined treatment (with more conventional drugs) for AHF patients.
Association between antioxidant status and MnSOD Ala-9Val polymorphism in trained male athletes (rugby players) and sedentary male students controlled for antioxidant intake
(Stellenbosch : Stellenbosch University, 2007-03) Seele, Maria; Senekal, M.; Steyn, N. P.; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: The human body has developed an integrated antioxidant defence system to protect against free radical damage. Acute exercise may result in the increased generation of free radicals, including reactive oxygen species, and this may overwhelm antioxidant defence systems resulting in oxidative stress. However, it has been shown that individuals who undergo regular exercise training may have improved antioxidant capacity when compared to sedentary controls. Results from research regarding the association between antioxidant capacity and exercise training are however not conclusive and further investigation is required. Therefore, the aim of this study was to investigate the association between the total plasma antioxidant status and selected plasma indicators of antioxidant status and the MnSOD Ala-9Val (-28C®T) polymorphism in trained male athletes (rugby players) and sedentary male students while controlling for dietary intake of the major antioxidants using a validated dietary assessment method. In order to address the potential confounding effect of dietary antioxidant intake on antioxidant status in the main study, a FFQ that measures vitamin C, vitamin E, carotenoid and flavonoid intake was developed. The reproducibility was assessed by the repeat administration of the FFQ (n = 38), while the va lidity was assessed using a 28-day closeended dietary record and repeated plasma vitamin C values (n = 18). Several statistical tests were conducted to compare the values obtained from the FFQ with values obtained from the various reference methods. While results from Bland-Altman plots suggested that the reproducibility and validity of FFQ was not completely satisfactory, similar mean values, moderate to strong correlation coefficients, and a high percentage of individuals classified correctly according to quartiles of intake indicated satisfactory reproducibility and validity of the FFQ in assessing antioxidant intake. Furthermore, moderate to strong validity coefficients obtained from the method of triads also indicated satisfactory validity for the FFQ. The main study involved a cross-sectional study that compared plasma vitamin C and carotenoid levels as well as total plasma antioxidant status in trained rugby players (n = 76) and sedentary male subjects (n = 39) with different MnSOD genotypes, while controlling for dietary antioxidant intake. Rugby players had significantly higher plasma vitamin C and carotenoid levels compared to sedentary students, which indicated more satisfactory plasma antioxidant status. This was also reflected in the tendency for total plasma antioxidant status (ORAC assay) to be higher in rugby players than sedentary students. MnSOD genotype did not influence plasma vitamin C and carotenoid levels or plasma total antioxidant status, with or without control for dietary antioxidant intake. Dietary vitamin C, vitamin E, carotenoid an flavonoid intake (from foods + supplements) was similar for rugby players and sedentary students and was adequate for both groups. Thus the association between antioxidant status and MnSOD genotype in rugby players and sedentary students seemed not to be influenced by dietary antioxidant intake. In conclusion therefore, rugby players undergoing regular exercise training had a more satisfactory antioxidant status compared to sedentary students. Based on this conclusion, the widespread use of antioxidant supplements by athletes is questioned.
Association between cancer, adipose tissue and selected systemic markers : a possible classification according to body shape
(Stellenbosch : Stellenbosch University, 2016-03) Mentoor, Ilze Lauren; Nell, Theo A.; Kruger, Maritza J.; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Background: The metabolic syndrome (MetS) is a cluster of risk factors associated with an increased risk of developing chronic diseases of lifestyle, and has more recently been associated with cancer risk. Currently, the pathophysiology of the MetS and cancer risk is still unknown; however it is proposed to involve several factors. These include the effects of body composition (android and gynoid shapes), and insulin resistance on the bioavailability of growth factors, inflammatory markers and sex hormone profiles. Various anthropometrical measurements have been used to investigate body composition, however, due to their limitations, a new metric namely a body shape index (ABSI) has been proposed to be a better measure of fat distribution and body shape. Aims: To determine the prevalence of the MetS, and the possible risks of developing cancer in relation to metabolic status, body composition, growth factors as well as inflammatory and sex hormone parameters. Methods: Female participants between the ages of 20-60 years were classified according to the International Diabetes Federation’s (IDF) definition of the MetS and according to body shape (android/gynoid) by photoscopic somatotyping. A series of tests and assessments were conducted; such as blood pressure assessments, anthropometric measurements, bioelectrical impedance analyses (BIA) and blood analyses. Blood analysis included fasting glucose, fasting insulin, lipid profile, insulin-like growth factor-1 (IGF-1), inflammatory marker (C-reactive protein (CRP)); and sex hormone parameters (oestrogen, female testosterone, sex hormone binding globulin; and free androgen index). Results: The prevalence of the MetS was found to be 57.5 %; with abdominal obesity (73.8 %), elevated blood pressure (BP, 68.8 %) and low high density lipoprotein-cholesterol (HDL-c) levels (68.8 %) being the more prevalent risk factors. Both metabolic status; and body shape alone were found to be predictors influencing anthropometric, BIA, physiological and biochemical blood parameters. Metabolic status was found to have an effect on several parameters in the gynoid body shape groups, i.e. body mass (BM) (p<0.001), hip circumference (HC) (p<0.01), body mass index (BMI) (p<0.001), fat mass (FM) (%) (p<0.01), fat free mass (FFM) (%) (p<0.01), waist circumference (WC) (p<0.001), HDL-c (p<0.001), triglycerides (TG) (p<0.05), systolic blood pressure (SBP) (p<0.05) and diastolic blood pressure (DBP) (p<0.01), while metabolic status showed an effect on BM (p<0.001), BMI (p<0.01), TG (p<0.05), SBP (p<0.01) and DBP (p<0.01) in the android body shape groups. Both metabolic status and body shape did not show any effect on ABSI, total cholesterol (TC), low density lipoprotein-cholesterol (LDL-c), fasting insulin, CRP and all sex hormone parameters. Correlation analyses revealed significant correlations for several anthropometric, BIA and blood parameters. Conclusion: This study showed that metabolic status, body shape and/or both could predict changes in various body composition, physiological and biochemical parameters in women. However, no effects were evident for any parameters linking the MetS to cancer risk. Thus, no accurate conclusion could be drawn regarding the pathophysiology. Our findings on ABSI, still warrants future investigation to substantiate the use of this metric in relation to the MetS, body shape and cancer risk.
The association between genotype and BMI, health and lifestyle indicators as well as weight loss outcomes in overweight/obese Caucasian adults
(Stellenbosch : University of Stellenbosch, 2011-03) Harbron, Janetta; Senekal, Marjanne; Zaahl, Monique; Kotze, Maritha J.; University of Stellenbosch. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Genetic screening to improve obesity treatment outcomes is available despite the lack of conclusive evidence, specifically for Caucasian South Africans, in this regard. The aim of this study was to investigate the association between genotype (seven polymorphisms) and body mass index (BMI), health and lifestyle indicators in a cross-sectional sample of overweight/obese Caucasian adults (n=133), as well as the association between genotype and weight loss outcomes following an intervention (n=88) using a quasi experimental study design (time-series). The intervention consisted of a 24-week conservative weight loss programme that included dietary, physical activity and behavioural components. The primary null hypothesis for the cross-sectional sample, namely that there is no association between genotype and BMI, has not been rejected. A number of the secondary/exploratory hypotheses were rejected of which the most plausible associations (based on support by the literature and a physiological basis for the findng) are: 1) the mutant TT homozygotes of the GNB3 C825T polymorphism may have a higher risk to develop the metabolic syndrome (MetS) as they had significantly higher fasting triglyceride and glucose levels, a higher number of traits that met the diagnostic cut-off criteria for MetS and higher number of these subjects was diagnosed with MetS compared to the wild-type C-allele carriers; and 2) subjects with mutant alleles of either the FTO rs1421085 or rs17817449 polymorphisms may have poorer eating behaviours (a higher rigid control, habitual and emotional disinhibition, perceived hunger and internal locus for hunger) and higher intake of high-fat foods. The primary null hypothesis for the intervention sample, namely that there is no association between genotype and weight loss outcome, was not rejected for the FABP2 Ala54Thr, INSIG2 rs7566605, FTO rs1421085, ADRB3 Trp64Arg and GNB3 C825T polymorphisms. However, it was rejected in some instances indicating the following associations: 1) The wild-type TT homozygotes of the FTO rs17817449 polymorphism lost significantly more weight during the first two months of the program compared to the mutant allele carriers (this is a novel finding); 2) The wild-type Arg16Arg homozygotes of the ADRB2 Arg16Gly polymorphism lost significantly more weight during the first month of the program compared to the mutant allele carriers (this finding is supported by one other intervention study); 3) Subjects with a mutant C-allele of the INSIG2 rs7566605 polymorphism and a mutant Gly16-allele of the ADRB2 Arg16Gly polymorphism lost significantly less weight over the six month intervention period (this is a novel genegene interaction finding). A number of secondary/exploratory hypotheses were rejected, of which the most plausible finding include that the improvement in emotional disinhibition in the wild-type TT subjects of the FTO rs1421085 polymorphism was associated with a more pronounced decrease in BMI over the six month weight loss period. The integration of the results from this study with the literature indicates that there is insufficient evidence at this stage for genetic screening of the polymorphisms investigated in this study and the provision of evidence-based personalized recommendations for weight loss in obese individuals. It is recommended that these associations should be viewed as priority in future research.
The association between the metabolic syndrome and bone mineral density in pre- and post-menopausal farm workers
(Stellenbosch : Stellenbosch University, 2016-12) Marais, Sumine; Nell, Theo A.; Kruger, Maritza J.; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Introduction and aims: The prevalence of the metabolic syndrome (MetS) is increasing, both globally and in South Africa. Albeit so, limited data have been published in the South African context. One of the factors that appear to influence the prevalence of the MetS is menopausal status, with both the MetS, and menopausal status influencing bone mineral density (BMD); however, the reported results are inconsistent. Therefore, the aim of this study was to determine the prevalence of the metabolic syndrome, investigating bone health as well as the interactions between the MetS, menopausal status and bone health, in a farm working female population in the Western Cape. Methods: A total of n=80 females were recruited and classified with the MetS, using the International Diabetes Federations’ definition. The data collected included basic anthropometric measurements, blood pressure, BMD, and several questionnaires to obtain information regarding physical activity, demographic information, menstrual-, diet- and family health- history. The blood parameters that were measured included alkaline phosphatase (ALP), vitamin D, parathyroid hormone (PTH), oestradiol (E2), fasting insulin (FI), fasting glucose (FG) and a lipid profile. Results: A relatively high prevalence of the MetS (55.0%) was reported in the current study. When investigating the separate MetS risk factors, most of the study participants had three risk factors (32.5%), with increased BP being the most prevalent MetS risk factor (72.5%). Factors that differed between MetS and Non-MetS sub-groups (according to menopausal status and age) included waist circumference (WC), high-density lipoprotein-cholesterol (HDL-c), systolic blood pressure (SBP) and diastolic blood pressure (DBP). Significant associations between body mass (BM) and E2, and body mass index (BMI) and E2, were limited to the PreM (20-39 years) age group with the MetS (r=0.58, p=0.03, and r=0.60, p=0.02). A total of 78.8% of the study participant had normal BMD. When correlating BM and speed of sound (SOS), significant associations were limited to the PreM (≥40 years) group (MetS: r=0.56, p=0.04, Non-MetS: r=0.76, p=0.00), and significant associations between BMI and SOS were noted in both PreM groups (MetS PreM 20-39 years: r=0.53, p=0.05, Non-MetS PreM ≥40 years: r=0.73, p=0.00). The significant correlations between FI and ALP (r=0.72, p=0.00), FG and ALP (r=0.89, p=0.00), and triglycerides with ALP (r=0.82, p=0.00) were limited to the PreM (≥40 years) group. Conclusion: The prevalence of the MetS was higher than that reported by previous South African studies. Irrespective of metabolic and menopausal status, most of the participants of the current study population had normal BMD. Key words: Metabolic syndrome, bone mineral density, menopause
Association between the metabolic syndrome and cancer risk : the potential role of fatty acids on body composition
(Stellenbosch : Stellenbosch University, 2016-12) Johnson, Olga; Nell, Theo A.; Kruger, Maritza; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
ENGLISH ABSTRACT: Background: Sub-Sahara Africa is experiencing an epidemiological transition with an increasing burden of non-communicable diseases (NCDs) including obesity, hypertension, insulin resistance (IR) and dyslipidaemia. These NCD are collectively labelled the metabolic syndrome (MetS). The MetS is characterised by dyslipidaemia, and in particular, distorted fatty acid (FA) metabolism. Additionally, the MetS and its components are also associated with different FA classes. Furthermore, several lifestyle-cancers have also been associated with the MetS and its components. Aim: To determine the association and interaction between the MetS and cancer risk and the likely influence of FAs on body composition in a female population residing in the Western Cape, South Africa. Methods: Female farm workers in the Cape Winelands region (n=80) aged 20-60 years were randomly selected and categorised as having the MetS (n=34 MetS and n=46 non-MetS) using the International Diabetes Federation (IDF) criteria. All participants were additionally classified according to their body mass index (BMI). Blood pressure was measured, followed by blood sampling to determine blood glucose and insulin levels, as well as a full lipid profile. Selected red blood cell (RBC) membrane FAs and FA ratios were analysed, and enzyme-linked immunosorbent assays (ELISAs) were used to quantify serum insulin-like growth factor-1 (IGF-1) and leptin concentrations. Anthropometric measurements and bioelectric impedance analyses (BIA) were also performed. Results: The prevalence of the MetS was 42.5 % with abdominal obesity (100.0 % for the MetS, and 39.1 % for the non-MetS), hypertension (82.4 % for the MetS, and 47.8 % for the non-MetS), and low high-density lipoprotein cholesterol (HDL-c) (76.5 % for the MetS, and 34.8 % for the non-MetS) being the most prevalent MetS risk factors. Several statistically significant differences were observed between the MetS and non-MetS groups for blood parameters, including insulin and HDL-c levels (p<0.001), and glucose, IGF-1, and leptin levels (p<0.05). The MetS group also presented with significantly higher anthropometric measurements, including BMI (p<0.05), waist circumference (WC), waist-to-hip ratio (W:H), and the sagittal abdominal diameter (SAD) (all p<0.001). Furthermore, BIA (including visceral adipose tissue (VAT) area, percentage VAT (VAT %) and -subcutaneous adipose tissue (SAT %), and VAT to SAT ratio (VAT:SAT) (p<0.001 for all) also differed between the MetS and non-MetS groups. No significant differences were noted for any of the individual FAs or FA ratios. Categorisation according to metabolic status and BMI was shown to influence several metabolic-associated blood parameters, anthropometric measurements, BIA. However, metabolic status and BMI did not influence individual FA levels or FA ratios. The obese MetS group presented with significantly higher IGF-1 levels compared to their normal weight non-MetS counterparts. Correlation analyses indicated several significant associations between anthropometric measurements, BIA, FAs and metabolic-associated blood parameters. Conclusion: The results from this study suggest that metabolic status alone, and the combined effect of metabolic status and BMI, may predict alterations in metabolic-associated blood parameters, anthropometric measurements, and BIA in women, possibly linking obesity and the MetS to an increased risk of developing lifestyle-associated cancer. Keywords Metabolic syndrome, fatty acid profile, body composition, leptin, cancer risk

Browse

Browsing Department of Physiological Sciences by Title

Results Per Page

Sort Options