Project description:Polycystic ovary syndrome (PCOS) is often associated with metabolic syndrome features, including central obesity, suggesting that adipose tissue (AT) is a key organ in PCOS pathobiology. In this study, we compared both abdominal (ABD) and gluteofemoral (GF) subcutaneous AT in women with and without PCOS. ABD and GF subcutaneous ATs from PCOS and BMI/WHR-matched control women were analyzed by RT-qPCR, FACS and histology. ABD and GF adipose-derived stem cell (ASC) transcriptome and methylome were analyzed by RNA-seq and DNA methylation array. Similar to the control group with abdominal obesity, the GF AT of PCOS women showed lower expression of genes involved in lipid accumulation and angiogenesis compared to ABD depot. FACS analysis revealed an increase in preadipocytes number in both AT depots from PCOS. Further pathway analysis of RNA-seq comparisons demonstrated that the ASCs derived from PCOS are pro-inflammatory and exhibit a hypoxic signature in the ABD depot and have lower expression of adipogenic genes in GF depot. We also found a higher CpG methylation level in PCOS compared to control exclusively in GF-ASCs. Our data suggest that ASCs play an important role in the etiology of PCOS, potentially by limiting expansion of the healthy lower-body AT.
Project description:In this data article, we present the dataset from the RNA-Seq analysis of subcutaneous adipose tissue collected from 5 healthy normal weight women (NW, age 37 ± 6.7 years, BMI 24.3 ± 0.9 kg/m2) and 5 obese women (OBF, age 41 ± 12.5 years, BMI 38.2 ± 4.6 kg/m2). Raw data obtained from Illumina NextSeq 500 sequencer were processed through BlueBee® Genomics Platform while differential expression analysis was performed with the DESeq2 R package and deposited in the GEO public repository with GSE166047 as accession number. Specifically, 20 samples divided between NW (control), OBF (obese women), OBM (obese male) and OBT2D (obese women with diabetes) are deposited in the GSE166047. We hereby describe only 10 samples (5 healthy normal weight women reported as NW and 5 obese women reported as OBF) because we refer to the data published in the article "Transcriptional characterization of Subcutaneous Adipose Tissue in obesity affected women highlights metabolic dysfunction and implications for lncRNAs" (DOI: 10.1016/j.ygeno.2021.09.014). Pathways analyses were performed on g:Profiler, Enrichr, ClueGO and GSEA to gain biological insights on gene expression. Raw data reported in GEO database along with detailed methods description reported in this data article could be reused for comparisons with other datasets on the topic to obtain transcriptional differences in a wider co-hort. Moreover, detailed pathways analysis along with cross-referenced data with other datasets will allow to identify novel dysregulated pathways and genes responsible for this regulation. The biological interpretation of this dataset, along with related in vitro experiments, is reported by Rey et al., in Genomics (DOI: 10.1016/j.ygeno.2021.09.014).
Project description:BackgroundThe central component of the complement system, C3, is associated with obesity, metabolic syndrome and cardiovascular disease however the underlying reasons are unknown. In the present study we evaluated gene expression of C3, the cleavage product C3a/C3adesArg and its cognate receptor C3aR in subcutaneous and omental adipose tissue in women.MethodsWomen (n = 140, 21-69 years, BMI 19.5-79 kg/m2) were evaluated for anthropometric and blood parameters, and adipose tissue gene expression.ResultsSubjects were separated into groups (n = 34-36) according to obesity: normal/overweight (≤30 kg/m2), obese I (≤45 kg/m2), obese II (≤51 kg/m2), and obese III (≤80 kg/m2). Overall, while omental expression remained unchanged, subcutaneous C3 and C3aR gene expression decreased with increasing adiposity (2-way ANOVA, p<0.01), with a concomitant decrease in SC/OM ratio (p<0.001). In subcutaneous adipose, both C3 and C3aR expression correlated with apoB, and apoA1 and inversely with waist circumference and blood pressure, while C3aR also correlated with glucose (p<0.05-0.0001). While omental C3aR expression did not correlate with any factor, omental C3 correlated with waist circumference, glucose and apoB (all p<0.05). Further, while plasma C3a/C3adesArg increased and adiponectin decreased with increasing BMI, both correlated (C3a negatively and adiponectin positively) with subcutaneous C3 and C3aR expression (p<0.05-0.001) or less).ConclusionsThe obesity-induced down-regulation of complement C3 and C3aR which is specific to subcutaneous adipose tissue, coupled to the strong correlations with multiple anthropometric, plasma and adipokine variables support a potential role for complement in immunometabolism.
Project description:Aims/hypothesisInflammation is associated with increased body mass and purportedly with increased size of adipose cells. We sought to determine whether increased size of adipose cells is associated with localised inflammation in weight-stable, moderately obese humans.MethodsWe recruited 49 healthy, moderately obese individuals for quantification of insulin resistance (modified insulin suppression test) and subcutaneous abdominal adipose tissue biopsy. Cell size distribution was analysed with a multisizer device and inflammatory gene expression with real-time PCR. Correlations between inflammatory gene expression and cell size variables, with adjustment for sex and insulin resistance, were calculated.ResultsAdipose cells were bimodally distributed, with 47% in a 'large' cell population and the remainder in a 'small' cell population. The median diameter of the large adipose cells was not associated with expression of inflammatory genes. Rather, the fraction of small adipose cells was consistently associated with inflammatory gene expression, independently of sex, insulin resistance and BMI. This association was more pronounced in insulin-resistant than insulin-sensitive individuals. Insulin resistance also independently predicted expression of inflammatory genes.Conclusions/interpretationThis study demonstrates that among moderately obese, weight-stable individuals an increased proportion of small adipose cells is associated with inflammation in subcutaneous adipose tissue, whereas size of mature adipose cells is not. The observed association between small adipose cells and inflammation may reflect impaired adipogenesis and/or terminal differentiation. However, it is unclear whether this is a cause or consequence of inflammation. This question and whether small vs large adipose cells contribute differently to inflammation in adipose tissue are topics for future research.Trial registrationClinicalTrials.gov NCT00285844.
Project description:BackgroundPrevious studies have documented that visceral adipose tissue is positively associated with the risk of diabetes. However, the association of subcutaneous adipose tissue with diabetes risk is still in dispute. We aimed to assess the associations between different adipose distributions and the risk of newly diagnosed diabetes in Chinese adults.MethodsThe Shanghai Nicheng Cohort Study was conducted among Chinese adults aged 45-70 years. The baseline data of 12,137 participants were analyzed. Subcutaneous and visceral fat area (SFA and VFA) were measured by magnetic resonance imaging. Diabetes was newly diagnosed using a 75 g oral glucose tolerance test.ResultsThe multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of newly diagnosed diabetes per 1-standard deviation increase in SFA and VFA were 1.29 (1.19-1.39) and 1.61 (1.49-1.74) in men, and 1.10 (1.03-1.18) and 1.56 (1.45-1.67) in women, respectively. However, the association between SFA and newly diagnosed diabetes disappeared in men and was reversed in women (OR 0.86 [95% CI, 0.78-0.94]) after additional adjustment for body mass index (BMI) and VFA. The positive association between VFA and newly diagnosed diabetes remained significant in both sexes after further adjustment for BMI and SFA. Areas under the receiver operating characteristic curve of newly diagnosed diabetes predicted by VFA (0.679 [95% CI, 0.659-0.699] for men and 0.707 [95% CI, 0.690-0.723] for women) were significantly larger than by the other adiposity indicators.ConclusionsSFA was beneficial for lower risk of newly diagnosed diabetes in women but was not associated with newly diagnosed diabetes in men after taking general obesity and visceral obesity into account. VFA, however, was associated with likelihood of newly diagnosed diabetes in both Chinese men and women.
Project description:The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.
Project description:The accumulation of fat in upper-body (abdominal) adipose tissue is associated with obesity-related cardiometabolic diseases, whereas lower-body (gluteal and femoral) fat may be protective. Studies suggest physiological and molecular differences between adipose depots and depot-specific cellular mechanisms of adipose expansion. We assessed in vivo cellular kinetics in subcutaneous adipose tissue from the abdominal (scABD) and femoral (scFEM) depots using an 8-week incorporation of deuterium ((2)H) from (2)H2O into the DNA of adipocytes and preadipocytes in 25 women with overweight or obesity. DNA synthesis rates denote new cell formation of preadipocytes and adipocytes in each depot. Formation of adipocytes was positively correlated to that of preadipocytes in the scABD and scFEM depots and was related to percent body fat in each depot. Notably, preadipocytes and adipocytes had higher formation rates in the scFEM depot relative to the scABD. This method to assess in vivo adipogenesis will be valuable to evaluate adipocyte kinetics in individuals with varying body fat distributions and degrees of metabolic health and in response to a variety of interventions, such as diet, exercise, or pharmacological treatment.