11 results on '"Kotzé-Hörstmann, Liske"'
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2. Hypoxia and extra-cellular matrix gene expression in adipose tissue associates with reduced insulin sensitivity in black South African women
- Author
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Kotzé-Hörstmann, Liske M., Keswell, Dheshnie, Adams, Kevin, Dlamini, Thandiwe, and Goedecke, Julia H.
- Published
- 2017
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3. Characterization and Comparison of the Divergent Metabolic Consequences of High-Sugar and High-Fat Diets in Male Wistar Rats.
- Author
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Kotzé-Hörstmann, Liske, Cois, Annibale, Johnson, Rabia, Mabasa, Lawrence, Shabalala, Samukelisiwe, Van Jaarsveld, Paul J., and Gijsen, Hanél Sadie-Van
- Subjects
HIGH-fat diet ,LABORATORY rats ,BODY composition ,LABORATORY rodents ,PRINCIPAL components analysis - Abstract
Diet-induced obesity (DIO) in laboratory rodents can serve as a model with which to study the pathophysiology of obesity, but obesogenic diets (high-sugar and/or high-fat) are often poorly characterised and simplistically aimed at inducing metabolic derangements for the purpose of testing the therapeutic capacity of natural products and other bioactive compounds. Consequently, our understanding of the divergent metabolic responses to different obesogenic diet formulations is limited. The aim of the present study was to characterise and compare differences in the metabolic responses induced by low-fat, medium-fat/high-sugar and high-fat diets in rats through multivariate statistical modelling. Young male Wistar rats were randomly assigned to CON (laboratory chow, low-fat), OB1 (high-sugar, medium-fat) or OB2 (high-fat) dietary groups (n = 24 each) for 17 weeks, after which metabolic responses were characterised. Projectionbased multivariate analyses (principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA)) were used to explore the associations between measures of body composition and metabolism. Furthermore, we conducted a systematic literature survey to examine reporting trends in rat dietary intervention studies, and to determine how the metabolic responses observed in the present study compared to other recently published studies. The OB1 and OB2 dietary regimens resulted in distinct metabolic profiles, with OB1 characterised by perturbations in insulin homeostasis and adipose tissue secretory function, while OB2 was characterised by altered lipid and liver metabolism. This work therefore confirms, by means of direct comparison, that differences in dietary composition have a profound impact on metabolic and pathophysiological outcomes in rodent models of DIO. However, through our literature survey we demonstrate that dietary composition is not reported in the majority of rat dietary intervention studies, suggesting that the impact of dietary composition is often not considered during study design or data interpretation. This hampers the usefulness of such studies to provide enhanced mechanistic insights into DIO, and also limits the translatability of such studies within the context of human obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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4. Effects of adipose tissue extracellular matrix components on body fat distribution and insulin sensitivity in black and white South African women
- Author
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Kotzé-Hörstmann, Liske, Goedecke, Julia, and Keswell, Dheshnie
- Abstract
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
- Published
- 2018
5. Modulation of Glucose Metabolism by Leaf Tea Constituents: A Systematic Review of Recent Clinical and Pre-clinical Findings
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Kotzé-Hörstmann, Liske M. and Sadie-Van Gijsen, Hanél
- Abstract
Leaf teas are widely used as a purported treatment for dysregulated glucose homeostasis. The objective of this study was to systematically evaluate the clinical and cellular-metabolic evidence, published between January 2013 and May 2019, and indexed on PubMed, ScienceDirect, and Web of Science, supporting the use of leaf teas for this purpose. Fourteen randomized controlled trials (RCTs) (13 on Camellia sinensisteas) were included, with mixed results, and providing scant mechanistic information. In contrast, 74 animal and cell culture studies focusing on the pancreas, liver, muscle, and adipose tissue yielded mostly positive results and highlighted enhanced insulin signaling as a recurring target associated with the effects of teas on glucose metabolism. We conclude that more studies, including RCTs and pre-clinical studies examining teas from a wider variety of species beyond C. sinensis, are required to establish a stronger evidence base on the use of leaf teas to normalize glucose metabolism.
- Published
- 2020
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6. An In Vivo/Ex Vivo Study Design to Investigate Effects of Chronic Conditions and Therapeutic Compounds on Adipose Stem Cells in Animal Models.
- Author
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Sadie-Van Gijsen H, Kotzé-Hörstmann L, and Huisamen B
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- Animals, Cell Culture Techniques, Humans, Models, Animal, Obesity drug therapy, Rats, Wistar, Research Design, Adipocytes drug effects, Adipose Tissue drug effects, Chronic Disease drug therapy, Pharmaceutical Preparations administration & dosage, Stem Cells drug effects
- Abstract
With the dramatic rise in the global prevalence of obesity and lack of success at addressing this public health issue, there is an urgency to develop new tools with which to study obesity and putative weight-loss products. Pre-adipocyte cell lines have been widely used as a model for adipocyte biology and obesity over the past four decades, but the applicability of results from these cell lines is limited. This chapter will describe an in vivo/ex vivo study design that can be employed to examine the effects of diets and other chronic physiological or pathophysiological conditions on the biology of adipose stem cells (ASCs), as a model for the progression and management of obesity. This type of study design is superior to short-term in vitro experiments in pre-adipocyte cell lines or ASCs, as chronic in vivo conditions cannot be recapitulated in cell culture. Rather, this in vivo/ex vivo study design provides researchers the opportunity to assess the progressive effects of long-term insults or interventions on the reprogramming of ASC behavior. In addition, this model allows us to study the metabolic effects of chronic conditions and therapeutic compounds at a systemic level as well as at the level of adipose tissue and ASCs, in order to provide a whole-body context for the findings.
- Published
- 2020
- Full Text
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