Cited by 60Ovarian function and disordersAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Impaired preadipocyte differentiation into adipocytes in subcutaneous abdominal adipose of PCOS-like female rhesus monkeys

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Keller, Erica, Chazenbalk, Gregorio D., Aguilera, Paul, Madrigal, Vanessa, Grogan, Tristan, Elashoff, David, Dumesic, Daniel A., Abbott, David H.·2014·Endocrinology

Abstract

Metabolic characteristics of polycystic ovary syndrome women and polycystic ovary syndrome-like, prenatally androgenized (PA) female monkeys worsen with age, with altered adipogenesis of sc abdominal adipose potentially contributing to age-related adverse effects on metabolism. This study examines whether adipocyte morphology and gene expression in sc abdominal adipose differ between late reproductive-aged PA female rhesus monkeys compared with age-matched controls (C). Subcutaneous abdominal adipose of both groups was obtained for histological imaging and mRNA determination of zinc finger protein 423 (Zfp423) as a marker of adipose stem cell commitment to preadipocytes, and CCAAT/enhancer binding protein (C/EBP)α/peroxisome proliferator-activated receptor (PPAR)δ as well as C/EBPα/PPARγ as respective markers of early- and late-stage differentiation of preadipocytes to adipocytes. In all females combined, serum testosterone (T) levels positively correlated with fasting serum levels of total free fatty acid (r(2) = 0.73, P < .002). PA females had a greater population of small adipocytes vs C (P < .001) in the presence of increased Zfp423 (P < .025 vs C females) and decreased C/EBPα (P < .003, vs C females) mRNA expression. Moreover, Zfp423 mRNA expression positively correlated with circulating total free fatty acid levels during iv glucose tolerance testing (P < .004, r(2) = 0.66), whereas C/EBPα mRNA expression negatively correlated with serum T levels (P < .02, r(2) = 0.43). Gene expression of PPARδ and PPARγ were comparable between groups (P = .723 and P = .18, respectively). Early-to-mid gestational T excess in female rhesus monkeys impairs adult preadipocyte differentiation to adipocytes in sc abdominal adipose and may constrain the ability of this adipose depot to safely store fat with age.

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References 53 · Cited by 60

Research works printed but not linked: 2

  1. [25]25. Goy RW, Robinson JA. Prenatal exposure of rhesus monkeys to patent androgens: morphological, behavioral, and physiological consequences. In: Hunt VR, Smith MK, Worth D, eds. Banbury Report II: Environmental Factors in Human Growth and Development. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory; 1982:355–378 [Google Scholar]
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Authors
Keller, E., Chazenbalk, G. D., Aguilera, P., Madrigal, V., Grogan, T., Elashoff, D., Dumesic, D. A., & Abbott, D. H.
Affiliations
  • University of California, Los Angeles (US)
  • University of Wisconsin–Madison (US)
Corresponding author
Chazenbalk, Gregorio D.
Venue
Endocrinology
Published
2014-07-01
Volume
155
Issue
7
Pages
2696-2703
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2153257786
Cited by
60
References
53
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 9 · 2019: 10 · 2018: 8 · 2017: 7 · 2016: 6 · 2015: 3 · 2014: 1
FWCI
6.88
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5u01hd044650-05, UL1TR000124, P51OD011106)
  • National Center for Research Resources (R01RR013635, P51RR000167)
  • National Center for Advancing Translational Sciences
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD071836, U01-HD044650, U54HD071836)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
polycystic ovary syndrome, prenatal androgen exposure, rhesus monkeys, subcutaneous abdominal fat, preadipocyte differentiation, adipogenesis, Zfp423, C/EBPα, PPARδ, PPARγ, testosterone, free fatty acids, adipocyte size, aging, glucose tolerance
MeSH terms
Androgens, Animals, Cell Differentiation, Female, Humans, Macaca mulatta, Polycystic Ovary Syndrome, Testosterone, Transcription Factors, Gene Expression, Zinc Fingers, Adipocytes, Reverse Transcriptase Polymerase Chain Reaction, CCAAT-Enhancer-Binding Protein-alpha, PPAR delta, PPAR gamma, Adipogenesis, Subcutaneous Fat, Abdominal

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