Ethnic differences in regional adipose tissue oestrogen receptor gene expression

Studies have shown ethnic differences in body fat distribution, characterised by greater peripheral and less central fat accumulation in black compared to white South African (SA) women. As sex hormones play an important role in body fat distribution, our study aimed to determine whether differences in body fat distribution between black and white SA women were associated with subcutaneous adipose tissue (SAT) expression of oestrogen receptors (ERA and ERB) and aromatase (CYP19A1). Body fat distribution (DXA and CT) and ERA, ERB and CYP19A1 expression in abdominal and gluteal SAT were measured in 26 black and 22 white SA women. Abdominal SAT ERA and ERB did not differ by ethnicity or BMI. Gluteal ERA was higher (1.08 ± 0.06 vs 0.99 ± 0.05, P < 0.001) and ERB was lower (0.99 ± 0.06 vs 1.10 ± 0.07, P < 0.001) in black vs white SA women. CYP19A1 increased with obesity in all depots (P < 0.001). In both black and white SA women, gluteal ERA was associated with lower central fat mass (FM) and greater gynoid FM (P < 0.05), while the inverse association was shown for CYP19A1 in all depots (P < 0.01). In conclusion, ethnic differences in gluteal ERA expression were associated with differences in body fat distribution previously reported between black and white SA women

Estimating the burden of disease attributable to excess body weight in South Africa in 2000

Objective. To estimate the burden of disease attributable to excess body weight using the  body mass index (BMI), by age and sex, in South Africa in 2000.Design. World Health Organization comparative risk assessment (CRA) methodology was followed. Re-analysis of the 1998 South Africa Demographic and Health Survey data provided mean BMI estimates by age and sex. Population attributable fractions were calculated and applied to revised burden of disease estimates. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis.Setting. South Africa.Subjects. Adults  ≥ 30 years of age.Outcome measures. Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ischaemic stroke, hypertensive disease, osteoarthritis, type 2 diabetes mellitus, and selected cancers. Results. Overall, 87% of type 2 diabetes, 68% of hypertensive disease, 61 % of endometrial cancer, 45% of ischaemic stroke, 38% of ischaemic heart disease, 31 % of  kidney cancer, 24% of osteoarthritis, 17% of colon cancer, and 13% of postmenopausal breast cancer were attributable to a BMI ≥ 21 kg/m2. Excess body weight is estimated to have caused 36 504 deaths (95% uncertainty interval 31 018 - 38 637) or 7% (95% uncertainty interval 6.0 - 7.4%) of all deaths in 2000, and 462 338 DALYs (95% uncertainty interval 396 512 - 478 847) or 2.9% of all DALYs (95% uncertainty interval 2.4 - 3.0%). The burden infemales was approximately double that in males.Conclusions. This study shows the importance of recognising excess body weight as a major risk to health, particularly among females, highlighting the need to develop, implement and evaluate comprehensive interventions to achieve lasting change in the determinants and impact of excess body weight

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution

Abstract Background Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. Methods We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. Results PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Conclusions Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk

DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance

CITATION: Willmer, T., et al. 2020. DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance. Clinical Epigenetics, 12:141, doi:10.1186/s13148-020-00932-3.The original publication is available at https://clinicalepigeneticsjournal.biomedcentral.comBackground: Disruption of the hypothalamic–pituitary–adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis. Methods: Abdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman’s correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA) expression and key indices of obesity and metabolic dysfunction. Results: Two CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese compared to normal weight women, while no differences in GR methylation were observed. Higher percentage methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference), insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic inflammation (c-reactive protein) in both adipose depots. GR and FKBP5 mRNA levels were lower in GSAT, but not ASAT, of obese compared to normal weight women. Moreover, FKBP5 mRNA levels were inversely correlated with DNA methylation and positively associated with adiposity, metabolic and inflammatory parameters. Conclusions: These findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and insulin resistance in South African women. Additional studies are required to assess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00932-3Publisher's versio

Socio-cultural, environmental and behavioural determinants of obesity in black South African women

South Africa (SA) is undergoing a rapid epidemiological transition and has the highest prevalence of obesity in sub- Saharan Africa (SSA), with black women being the most affected (obesity prevalence 31.8%). Although genetic factors are important, socio-cultural, environmental and behavioural factors, as well as the influence of socio-economic status, more likely explain the high prevalence of obesity in black SA women. This review examines these determinants in black SA women, and compares them to their white counterparts, black SA men, and where appropriate, to women from SSA. Specifically this review focuses on environmental factors influencing obesity, the influence of urbanisation, as well as the interaction with socio-cultural and socio-economic factors. In addition, the role of maternal and early life factors and cultural aspects relating to body image are discussed. This information can be used to guide public health interventions aimed at reducing obesity in black SA women.Department of HE and Training approved lis

Adiposity Mediates the Association Between the Dietary Inflammatory Index and Markers of Type 2 Diabetes Risk in Middle-Aged Black South African Women

The dietary inflammatory index (DII®), a validated tool used to measure the inflammatory potential of the diet, has been associated with metabolic disorders in various settings, but not in African populations. The aim of this study was to investigate whether the DII is associated with markers of type 2 diabetes (T2D) risk, and if this association is mediated by adiposity and/or low-grade inflammation, in black South Africa women. Energy-adjusted-DII (E-DII) scores were calculated in 190 women (median age, 53 years) from the Birth-to-Twenty plus cohort using a validated food frequency questionnaire. Fasting glucose, insulin, HbA1c, and inflammatory cytokines were measured, and an oral glucose tolerance test performed. Basic anthropometry and dual-energy x-ray absorptiometry-derived body fat, including estimate of visceral adipose tissue (VAT) area, were measured. E-DII scores were associated with all markers of T2D risk, namely, fasting glucose and insulin, HbA1c, HOMA2-IR, two-hour glucose and Matsuda index (all p \u3c 0.05). After adjusting for age, measures of adiposity, but not inflammatory cytokines, mediated the association between E-DII and markers of T2D risk (p \u3c 0.05). Measures of central obesity had proportionally higher (range: 23.5–100%) mediation effects than total obesity (range: 10–60%). The E-DII is associated with T2D risk through obesity, in particular central obesity, among black middle-aged South African women

Meeting physical activity guidelines is associated with reduced risk for cardiovascular disease in black South African women; a 5.5-year follow-up study

Background: Low levels of physical activity (PA) have been associated with increased risk for cardiovascular disease (CVD) and type 2 diabetes (T2D), but few studies have examined whether meeting international PA guidelines is associated with reduced risk in a black South African (SA) population. The aims of this study were to compare body composition and cardio-metabolic risk factors for CVD and T2D between active and inactive groups (part 1, cross-sectional analysis) and, to determine whether PA level predicts changes in body composition and cardio-metabolic risk factors for CVD and T2D at follow-up after 5.5-years (part 2, longitudinal analysis). Methods: Part 1 included a sample of 240 apparently healthy black SA women (26 ± 7 years) who underwent the following measurements at baseline: PA (Global Physical Activity Questionnaire (GPAQ)), body composition and regional fat distribution (dual-energy x-ray absorptiometry and computerised tomography), blood pressure, fasting glucose, insulin and lipid concentrations. For part 2, a sub-sample of women (n = 57) underwent the same measurements after a 5.5-year period. Results: At baseline, 61% of women were classified as meeting the guidelines for moderate- to vigorous-intensity physical activity (MVPA) according to GPAQ. Women who were active had significantly lower body weight (p < 0.001), body fat (BMI, fat mass, % body fat, waist circumference, central and appendicular fat mass, all p < 0.001), and measures of insulin resistance (fasting serum insulin and HOMA-IR, both p = 0.01), and higher high-density lipoprotein cholesterol (p = 0.041), compared to the inactive group. At follow-up, all body fat measures increased significantly in both groups and diastolic blood pressure decreased significantly in those who were active at baseline, but did not change in those who were inactive. Conclusions: Meeting PA guidelines was associated with decreased risk for CVD and T2D in black SA women, but did not prevent the increase in body fat over time. Interventions promoting physical activity to specifically address obesity in this high-risk group are recommended

Exercise intervention alters HDL subclass distribution and function in obese women

Background Obesity is associated with a change in high-density lipoprotein (HDL) function and subclass. Exercise training reduces cardiovascular risk in obese patients. We aimed to explore the effect of an exercise training stimulus on HDL functionality and subclass in obese women. Methods Thirty-two obese black South African women were randomly assigned to exercise (combined aerobic and resistance exercise) or control (no exercise) conditions for 12-weeks. Pre- and post-testing included venous blood sampling for analysis of lipid profile and HDL functionality, by measuring cellular cholesterol efflux capacity, reduction in endothelial vascular cell adhesion molecule (VCAM) expression (anti-inflammatory function), paraoxonase (PON) (antioxidative function) and platelet activating factor acetylhydrolase (PAF-AH) activities (anti-thrombotic function). PON-1 and PAF-AH expression were determined in serum and in isolated HDL using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. Results Exercise training resulted in a decrease in body mass index (− 1.0 ± 0.5% vs + 1.2 ± 0.6%, p = 0.010), PON activity (− 8.7 ± 2.4% vs + 1.1 ± 3.0%, p = 0.021), PAF-AH serum expression (− 22.1 ± 8.0% vs + 16.9 ± 9.8, p = 0.002), and the distribution of small HDL subclasses (− 10.1 ± 5.4% vs + 15.7 ± 6.6%, p = 0.004) compared to controls. Exercise did not alter HDL cellular cholesterol efflux capacity and anti-inflammatory function. Conclusions These results demonstrate the potential for exercise training to modify HDL subclass distribution and HDL function in obese women. Trial registration Clinical trials number: PACTR201711002789113

A pilot investigation of genetic and epigenetic variation of FKBP5 and response to exercise intervention in African women with obesity

We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the efect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n= 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n= 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratifed based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT (p < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory ftness, insulin sensitivity, gynoid fat mass, and waist circumference (p < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These fndings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a signifcant impact on responsiveness to exercise interventions.The South African Medical Research Council (SAMRC), the National Research Foundation professional development program (PDP), Tuthuka and the International Atomic Energy agency.https://www.nature.com/srepdm2022Obstetrics and Gynaecolog