Dataset Information

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass.

ABSTRACT: Menopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. In this cross-sectional study of 33 women between 45 and 60 years, we assessed adipose tissue inflammation and morphology in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) across menopause and related this to menopausal differences in adipose tissue distribution and insulin resistance. We collected paired SAT and VAT biopsies from all women and combined this with anthropometric measurements and estimated whole-body insulin sensitivity. We found that menopause was associated with changes in adipose tissue phenotype related to metabolic dysfunction. In SAT, postmenopausal women showed adipocyte hypertrophy, increased inflammation, hypoxia and fibrosis. The postmenopausal changes in SAT was associated with increased visceral fat accumulation. In VAT, menopause was associated with adipocyte hypertrophy, immune cell infiltration and fibrosis. The postmenopausal changes in VAT phenotype was associated with decreased insulin sensitivity. Based on these findings we suggest, that menopause is associated with changes in adipose tissue phenotype related to metabolic dysfunction in both SAT and VAT. Whereas increased SAT inflammation in the context of menopause is associated with VAT accumulation, VAT morphology is related to insulin resistance.

SUBMITTER: Abildgaard J

PROVIDER: S-EPMC8292317 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass.

Abildgaard Julie J Ploug Thorkil T Al-Saoudi Elaf E Wagner Thomas T Thomsen Carsten C Ewertsen Caroline C Bzorek Michael M Pedersen Bente Klarlund BK Pedersen Anette Tønnes AT Lindegaard Birgitte B

Scientific reports 20210720 1

Menopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. In this cross-sectional study of 33 women between 45 and 60 years, we assessed adipose tissue inflammation and morphology in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) across menopause and related this to menopausal differences in adipose tissue distribution and insulin resistance. We collected paired SAT and VAT biopsies from all women and combin ...[more]

PMID: 34285301

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Project description:Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.

Project description:The current study tested the hypothesis that glucose utilization differs between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated potential mechanisms for such a finding.VAT burden correlates better with cardiovascular risk than does SAT burden. Beyond volumetric measurement, glucose uptake in adipose tissue (AT) might reflect metabolic activity and provide pathophysiologic insight and aid risk stratification.We retrospectively studied tissue-specific glucose uptake in vivo in clinically obtained whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scans in humans. We also assessed glucose uptake in vitro, using stromal vascular cells isolated from SAT and VAT of diet-induced obese C57BL/6 mice. Quantitative polymerase chain reaction (PCR) evaluated the expression of multiple genes involved in cellular glucose metabolism, including glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2) in SAT and VAT of obese C57BL/6 mice.We analyzed whole-body FDG-PET scans from 31 obese and 26 lean patients. VAT exhibited higher FDG uptake compared with SAT (p < 0.0001) independent of age, sex, body mass index, comorbidities, and medications. To investigate mechanisms underlying this observation, we studied glucose uptake in the stromal vascular cell fraction of AT, which is rich in inflammatory cells. Stromal vascular cells from VAT of diet-induced obese C57BL/6 mice exhibited higher glucose uptake than those from SAT (p = 0.01). Evaluation of expression of glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2), revealed increased expression of HK-1 in VAT-derived compared with SAT-derived stromal vascular cells, and also in visceral versus subcutaneous unfractionated AT.In humans in vivo, VAT has increased glucose uptake compared with SAT, as determined noninvasively with FDG PET imaging. Differential stromal metabolic activity may be 1 mechanism underlying differences in metabolic activity of visceral and subcutaneous AT.

Dataset Information

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass.

Publications

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass.

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