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Cited by 116Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

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

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Abildgaard, Julie, Ploug, Thorkil, Al-Saoudi, Elaf, Wagner, Thomas, Thomsen, Carsten, Ewertsen, Caroline, Bzorek, Michael, Pedersen, Bente Klarlund, Pedersen, Anette Tønnes, Lindegaard, Birgitte·2021·Scientific Reports
DOI 10.1038/s41598-021-94189-2PMC PMC8292317
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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.

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Crossref · 10.1038/s41598-021-94189-2

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Figure 1 Adipocyte size and mRNA expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in pre- (SAT, n = 10; VAT, n = 12), peri- (SAT and VAT, n = 5), and postmenopausal women (SAT, n = 12; VAT, n = 14). (A) Adipocyte size distribution in SAT in pre-, peri-, and postmenopausal women, (B) Adipocyte size distribution in VAT, (C) Representative HE-section of SAT and VAT, (D) Adipocyte size in SAT and VAT, (E) Adipocyte number in SAT and VAT, (F) Adipocyte number per kg fat in SAT and VAT, (G) mRNA expression of Peroxisome Proliferator-Activated Receptor (PPAR)-γ, Fatty Acid Synthase (FAS), Steraoyl-CoA Desaturase (SCD)1, Hypoxia-inducible factor (HIF)-1α, Vascular Endothelial Growth Factor A (VEGFA), Estrogen Receptor 1 (ESR1), and Adiponectin (AdipoQ) in both SAT and VAT. Data are presented as median (interquartile range). *Significant difference, p < 0.05.
Figure 1 Adipocyte size and mRNA expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in pre- (SAT, n = 10; VAT, n = 12), peri- (SAT and VAT, n = 5), and postmenopausal women (SAT, n = 12; VAT, n = 14). (A) Adipocyte size distribution in SAT in pre-, peri-, and postmenopausal women, (B) Adipocyte size distribution in VAT, (C) Representative HE-section of SAT and VAT, (D) Adipocyte size in SAT and VAT, (E) Adipocyte number in SAT and VAT, (F) Adipocyte number per kg fat in SAT and VAT, (G) mRNA expression of Peroxisome Proliferator-Activated Receptor (PPAR)-γ, Fatty Acid Synthase (FAS), Steraoyl-CoA Desaturase (SCD)1, Hypoxia-inducible factor (HIF)-1α, Vascular Endothelial Growth Factor A (VEGFA), Estrogen Receptor 1 (ESR1), and Adiponectin (AdipoQ) in both SAT and VAT. Data are presented as median (interquartile range). *Significant difference, p < 0.05.CC BY · PubMed Central
Figure 2 Morphology and inflammation in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in pre- (SAT, n = 10; VAT, n = 12), peri- (SAT and VAT, n = 5), and postmenopausal women (SAT, n = 12; VAT, n = 14). (A) Number of CD163+ cells/100 adipocytes in SAT and VAT in pre-, peri-, and postmenopausal women, (B) Number of CD68+ cells/100 adipocytes in SAT and VAT, (C) Number of CD3+ cells/100 adipocytes in SAT and VAT, (D) Number of CD20+ cells/100 adipocytes in SAT and VAT, (E) Pericellular fibrosis (PcF)/100 adipocytes in SAT and VAT, (F) Representative immunohistochemistry- and counter stainings of SAT and VAT, (G) mRNA expression of interleukin (IL)-6, IL-18, Tumor Necrosis Factor (TNF)-α, and Monocyte Chemoattractant Protein (MCP)-1, in SAT and VAT. Data are presented as median (interquartile range). *Significant difference, p < 0.05. #Significant difference between SAT and VAT, p < 0.05.
Figure 2 Morphology and inflammation in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in pre- (SAT, n = 10; VAT, n = 12), peri- (SAT and VAT, n = 5), and postmenopausal women (SAT, n = 12; VAT, n = 14). (A) Number of CD163+ cells/100 adipocytes in SAT and VAT in pre-, peri-, and postmenopausal women, (B) Number of CD68+ cells/100 adipocytes in SAT and VAT, (C) Number of CD3+ cells/100 adipocytes in SAT and VAT, (D) Number of CD20+ cells/100 adipocytes in SAT and VAT, (E) Pericellular fibrosis (PcF)/100 adipocytes in SAT and VAT, (F) Representative immunohistochemistry- and counter stainings of SAT and VAT, (G) mRNA expression of interleukin (IL)-6, IL-18, Tumor Necrosis Factor (TNF)-α, and Monocyte Chemoattractant Protein (MCP)-1, in SAT and VAT. Data are presented as median (interquartile range). *Significant difference, p < 0.05. #Significant difference between SAT and VAT, p < 0.05.CC BY · PubMed Central

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Authors
Abildgaard, J., Ploug, T., Al-Saoudi, E., Wagner, T., Thomsen, C., Ewertsen, C., Bzorek, M., Pedersen, B. K., Pedersen, A. T., & Lindegaard, B.
Affiliations
  • University of Copenhagen (DK)
  • Copenhagen University Hospital (DK)
  • Zealand University Hospital (DK)
Corresponding author
Abildgaard, Julie
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-07-20
Volume
11
Issue
1
Pages
14750-14750
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-94189-2
PMC
PMC8292317
OpenAlex
W3184145417
Cited by
116
References
62
Citations by year
2026: 38 · 2025: 33 · 2024: 14 · 2023: 19 · 2022: 11 · 2021: 1
FWCI
8.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Augustinus Fonden (17-2354)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
menopause, subcutaneous adipose tissue, visceral adipose tissue, adipose tissue inflammation, adipocyte hypertrophy, adipose tissue fibrosis, adipose tissue hypoxia, immune cell infiltration, insulin resistance, visceral fat accumulation, adipose tissue redistribution, abdominal obesity, postmenopausal women
MeSH terms
Aging, Female, Humans, Inflammation, Insulin, Insulin Resistance, Menopause, Middle Aged, Phenotype, Metabolic Syndrome, Peroxisome Proliferator-Activated Receptors, Estrogen Receptor alpha, Intra-Abdominal Fat, Body Fat Distribution, Subcutaneous Fat, Abdominal

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