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

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tarryn Willmer ◽  
Julia H. Goedecke ◽  
Stephanie Dias ◽  
Johan Louw ◽  
Carmen Pheiffer
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
South African ◽  
Hpa Axis ◽  
Normal Weight ◽  
African Women ◽  
Mrna Levels ◽  
South African Women ◽  
Subcutaneous Adipose

Abstract Background 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. Graphical abstract

scholarly journals Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 410 ◽  
Author(s):  
Daniel Castellano-Castillo ◽  
Isabel Moreno-Indias ◽  
Jose Carlos Fernandez-Garcia ◽  
Mercedes Clemente-Postigo ◽  
Manuel Castro-Cabezas ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Messenger Rna ◽  
Density Lipoprotein ◽  
Complement Factor ◽  
Mrna Levels ◽  
Model Assessment ◽  
Tissue Samples ◽  
Obese Class

Epigenetic marks, and especially DNA methylation, are becoming an important factor in obesity, which could help to explain its etiology and associated comorbidities. Adipose tissue, now considered as an important endocrine organ, produces complement system factors. Complement component 3 (C3) turns out to be an important protein in metabolic disorders, via either inflammation or the C3 subproduct acylation stimulating protein (ASP) which directly stimulates lipid storage. In this study, we analyze C3 DNA methylation in adipose tissue from subjects with a different grade of obesity. Adipose tissue samples were collected from subjects with a different degree of obesity determined by their body mass index (BMI) as: Overweight subjects (BMI ≥ 25 and <30), obese class 1/2 subjects (BMI ≥ 30 and <40) and obese class 3 subjects (BMI ≥ 40). C3 DNA methylation was measured for 7 CpGs by pyrosequencition using the Pyromark technology (Qiagen, Madrid Spain). C3 messenger RNA (mRNA) levels were analyzed by pre-designed Taqman assays (Applied biosystems, Foster City, CA, USA) and ASP/C3a was measured using a ELISA kit. The data were analyzed using the statistic package SPSS. C3 DNA methylation levels were lower in the morbid obese group. Accordingly, C3 methylation correlated negatively with BMI and leptin. However, C3 mRNA levels were more associated with insulin resistance, and positive correlations with insulin, glucose and homeostasis model assessment-estimated insulin resistance (HOMA-IR) existed. ASP correlated negatively with high density lipoprotein (HDL) cholesterol. C3 methylation levels were associated to adiposity variables, such as BMI and leptin, while the C3 mRNA levels were associated to glucose metabolism.

scholarly journals Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus

2019 ◽  
Vol 20 (23) ◽  
pp. 5828 ◽  
Author(s):  
Stephanie Dias ◽  
Sumaiya Adam ◽  
Paul Rheeder ◽  
Johan Louw ◽  
Carmen Pheiffer
Keyword(s):  
Diabetes Mellitus ◽  
Dna Methylation ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
South African ◽  
Peripheral Blood ◽  
African Women ◽  
Genome Wide ◽  
South African Women ◽  
Methylation Patterns

Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of differentially methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes) were differentially methylated between GDM and non-GDM groups. Enriched pathways included GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate insulin production and secretion and may offer potential as an epigenetic biomarker in our population. Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes and in different populations are required to investigate their candidacy as biomarkers of GDM.

scholarly journals The discriminatory power of visceral adipose tissue area vs anthropometric measures as a diagnostic marker for metabolic syndrome in South African women

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Florence E. Davidson ◽  
Tandi E. Matsha ◽  
Rajiv T. Erasmus ◽  
Andre Pascal Kengne ◽  
Julia H. Goedecke
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
High Risk ◽  
South African ◽  
Visceral Adipose Tissue ◽  
African Women ◽  
Anthropometric Measures ◽  
Cut Points ◽  
South African Women ◽  
Visceral Adipose

Abstract Background A number of studies have shown central adiposity, in particular visceral adipose tissue (VAT) accumulation to be a hallmark of metabolic syndrome (MetS). In clinical practice, waist circumference (WC) is used as a proxy for VAT. Aim To compare the ability of dual energy x-ray absorptiometry (DXA)-derived VAT area and anthropometric measures of adiposity for diagnosing MetS in a sample of high risk South African women. Methods MetS was quantified using the Joint Interim Statement (JIS) criteria. Fasting glucose, insulin and lipid profile were measured in 204 post-menopausal women. Anthropometry measures included body mass index (BMI), WC, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and a body shape index (ABSI). The area under the curve (AUC) was used to assess their performance in detecting any two components of MetS (excluding WC). Optimal WC and VAT area cut-points were derived to compare their performance for diagnosing MetS and to compare to internationally recognised cut-points. Results The highest AUC for the prediction of MetS was recorded for VAT, followed by WHtR and WC (AUC, 0.767, 0.747 and 0.738 respectively), but these did not differ significantly (all p ≥ 0.192). In contrast, VAT was significantly better than BMI (p = 0.028), hip (p = 0.0004) and ABSI (p < 0.0001). The optimal WC (94.4 cm) and VAT area (174 cm2 based on the Youden’s index method and 175.50 cm2 based on the CTL approach) cut-points performed similarly in detecting MetS. Conclusion DXA-derived VAT and WC had the same overall performance in discriminating the presence of any 2 MetS components in high risk South African women. These findings support the current recommendations of using WC rather than VAT for MetS risk screening, as it is cheap, accessible and easy to measure.

scholarly journals The association of interleukin-18 genotype and serum levels with metabolic risk factors for cardiovascular disease

2007 ◽  
Vol 157 (5) ◽  
pp. 633-640 ◽  
Author(s):  
Juliet Evans ◽  
Malcolm Collins ◽  
Courtney Jennings ◽  
Lize van der Merwe ◽  
Ingegerd Söderström ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
South African ◽  
Normal Weight ◽  
Visceral Adiposity ◽  
Metabolic Risk Factors ◽  
African Women ◽  
Metabolic Risk ◽  
Black South African ◽  
South African Women

AbstractObjectiveCirculating levels of interleukin (IL)-18 are associated with the metabolic syndrome and risk for the development of cardiovascular disease (CVD). This study investigated the association between the circulating IL-18 levels and the −137 G/C polymorphism within the IL-18 gene with metabolic risk factors for CVD in normal-weight and obese black South African women.MethodsBlood pressure (BP), body composition (dual-energy X-ray absorptiometer), visceral adiposity (computerized tomography), as well as fasting glucose, insulin, lipid profile, IL-18 levels, and IL-18 genotype were measured in 104 normal-weight (body mass index (BMI) ≤25 kg/m2) and 124 obese (BMI≥30 kg/m2) black South African women.ResultsSubjects with a GC genotype (23%) had a greater mean arterial pressure (MAP, 90.6±11.1 vs 85.5±10.3 mmHg, P<0.001) than the subjects with the GG genotype. Serum IL-18 levels were not associated with IL-18 genotype (P=0.985); however, they significantly correlated with percentage of body fat (r=0.25, P<0.001), visceral adiposity (r=0.32, P<0.001), MAP (r=0.22, P=0.001), HOMA-IR (r=0.33, P<0.001), fasting insulin (r=0.25, P<0.001), triglyceride (r=0.16, P<0.05), and high-density lipoprotein-cholesterol (r=−0.14, P<0.05) levels, after adjusting for age and body fatness.ConclusionsWe show for the first time that the GC genotype of the IL-18 −137 G/C polymorphism and the circulating IL-18 levels are independently associated with raised BP. Moreover, fasting IL-18 levels are associated with the other metabolic risk factors for CVD in normal-weight and obese black South African women.

scholarly journals Circulating and Adipose Tissue Fatty Acid Composition in Black South African Women with Obesity: A Cross-Sectional Study

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1619
Author(s):  
Pamela A. Nono Nankam ◽  
Paul J. van Jaarsveld ◽  
Elin Chorell ◽  
Melony C. Fortuin-de Smidt ◽  
Kevin Adams ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
South African ◽  
Body Fat ◽  
Unsaturated Fatty Acids ◽  
African Women ◽  
Black South African ◽  
Fa Composition ◽  
South African Women

Background and Aims: During positive energy balance, excess lipid storage in subcutaneous adipose tissue (SAT) is associated with increased lipolysis. Elevated circulating fatty acid (FA) concentrations from both SAT lipolysis and dietary fat intake may result in visceral adipose tissue (VAT) accumulation, impairment of glucose metabolism, altogether increasing obesity-associated metabolic risks. We aimed to test the hypothesis that FA composition of red blood cell total phospholipids (RBC-TPL) and SAT is associated with body fat centralisation (VAT/SAT ratio) and insulin sensitivity (SI) in black South African women with obesity. Methods: Participants’ (n = 41) body fat composition and distribution, SI, and RBC-TPL, abdominal and gluteal SAT (gSAT) FA composition (gas-liquid chromatography) were measured. Results: RBC-TPL contained higher proportions of saturated fatty acids (SFAs) than SAT (p < 0.001), which were associated with lower SI (p < 0.05). Mono-unsaturated fatty acids (MUFAs) and stearoyl-CoA desaturase-1 (SCD1)-16 were lower, while poly-unsaturated fatty acids (PUFAs), and delta-5 and delta-6 desaturase indices were higher in RBC-TPL than SAT (p < 0.001). Interestingly, FA profiles differed between SAT depots with higher SFAs and lower MUFAs, SCD1-16 and SCD1-18 indices in abdominal compared to gluteal SAT (p < 0.01). In both SAT depots, higher SFAs and lower PUFAs (n-3 and n-6) correlated with lower VAT/SAT ratio; and lower PUFAs (n-3 and n-6) and higher total MUFA correlated with higher SI. Conclusion: Our findings confirm the relationships between the FA composition of RBC-TPL and SAT and metabolic risk in black women with obesity, which are dependent on both the FA class, and the tissue type/blood compartment in which they are distributed.

Associations between long self-reported sleep, obesity and insulin resistance in a cohort of premenopausal Black and White South African women

Sleep Health ◽  
2018 ◽  
Vol 4 (6) ◽  
pp. 558-564 ◽  
Author(s):  
Dale E. Rae ◽  
Paula R. Pienaar ◽  
Rob H.P. Henst ◽  
Laura C. Roden ◽  
Julia H. Goedecke
Keyword(s):  
Insulin Resistance ◽  
South African ◽  
African Women ◽  
Black And White ◽  
South African Women

scholarly journals Differential Effects of Abdominal Adipose Tissue Distribution on Insulin Sensitivity in Black and White South African Women

Obesity ◽  
2009 ◽  
Vol 17 (8) ◽  
pp. 1506-1512 ◽  
Author(s):  
Julia H. Goedecke ◽  
Naomi S. Levitt ◽  
Estelle V. Lambert ◽  
Kristina M. Utzschneider ◽  
Mirjam V. Faulenbach ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Tissue Distribution ◽  
South African ◽  
African Women ◽  
Abdominal Adipose Tissue ◽  
Differential Effects ◽  
Black And White ◽  
Adipose Tissue Distribution ◽  
South African Women

scholarly journals Nutrient Patterns and Body Composition Parameters of Black South African Women

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 6
Author(s):  
Caroline B. T. Makura-Kankwende ◽  
Philippe J. Gradidge ◽  
Nigel J. Crowther ◽  
Shane A. Norris ◽  
Tinashe Chikowore
Keyword(s):  
Body Composition ◽  
Adipose Tissue ◽  
South African ◽  
Body Fat ◽  
Lean Mass ◽  
African Women ◽  
Whole Body ◽  
Black South African ◽  
Nutrient Patterns ◽  
South African Women

Obesity is more prevalent in black South African women than men. However, little is known about the nutrient patterns associated with body composition indices in black African women. Principle Component Analysis (PCA) was applied to 25 nutrients derived from quantified food frequency questionnaires (QFFQs) in 498 middle aged black South African women. Three nutrient patterns, the plant driven, animal driven and Vitamin C, sugar and potassium driven nutrient patterns, accounted for 59% of the variance of nutrient intake. Linear models of the body composition parameters as outcome variables indicated that a standard deviation increase in the animal driven nutrient pattern was significantly associated with increases in body mass index (BMI) (1.29 kg·m−2 (95% CI, 0.54–2.04; p = 0.001), subcutaneous adipose tissue (SAT) (26.30 cm2 (7.97–44.63); p = 0.005), visceral adipose tissue (VAT) (9.88 cm2 (5.13–14.63); p < 0.001), VAT/SAT ratio (0.01 (0.00–0.02); p = 0.018), whole body fat mass index (0.74 kg·m−2 (0.25–1.22); p = 0.003), and whole body lean mass index (0.53 kg·m−2 (0.23–0.83); p = 0.001). An increase in plant driven nutrient pattern was significantly associated with an increase in SAT of 20.45 cm2 (0.47–40.43); p = 0.045. This study demonstrates that animal driven nutrient pattern, characterised by the consumption of more animal protein and fat nutrients, similar to the western diet is associated with increased body fat and lean mass.

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