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Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome

International Journal of Obesity volume 31, pages 1579–1585 (2007)Cite this article

Abstract

Introduction:

Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with polycystic ovary syndrome (PCOS) women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic β-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI).

Objective:

To determine whether PA females have altered body fat distribution.

Design:

Five early-treated PA (EPA), five late-treated PA (LPA) and five control adult female monkeys underwent somatometrics, dual-X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and five EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation.

Results:

There were no differences in age, weight, BMI or somatometrics. LPA females had ∼20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (P⩽0.05). LPA females also had ∼40% more CT-determined non-visceral abdominal fat than EPA or control females (P⩽0.05). The volume of visceral fat was similar among the three groups. EPA (R2=0.94, P⩽0.01) and LPA (R2=0.53, P=0.16) females had a positive relationship between visceral fat and BMI, although not significant for LPA females. Conversely, control females had a positive relationship between non-visceral fat and BMI (R2=0.98, P⩽0.001). There was a positive relationship between basal insulin and total body (R2=0.95, P⩽0.007), total abdominal (R2=0.81, P⩽0.04) and visceral (R2=0.82, P⩽0.03) fat quantities in EPA, but not control females.

Conclusions:

Prenatal androgenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women.

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Acknowledgements

We gratefully acknowledge Mike Dobbert, Jim Turk, Kerri Hable, Peggy Helwig, Amy Lange, John Garry, Deborah Barnett, PhD, Kurt Sladky, DVM, and Lisa Forrest, DVM for assistance with procedures. We also thank Ron Gangnon and Mike Evans for statistical support, Fritz Wegner and the Assay Services of WNPRC for assay support, and the veterinary and animal care staff at WNPRC. This work was supported by NIH grants R01 RR013635, T32 AG000268, P50 HD044405 and P51 RR000167. This research was conducted at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459 and RR020141.

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Authors and Affiliations

  1. Dean Clinic, Madison, WI, USA

    C M Bruns

  2. Center for Women's Health Research, University of Wisconsin, Madison, WI, USA

    C M Bruns

  3. National Primate Research Center, University of Wisconsin, Madison, WI, USA

    S T Baum, R J Colman, D A Dumesic, J R Eisner, L D Whigham & D H Abbott

  4. Institute on Aging, University of Wisconsin, Madison, WI, USA

    R J Colman

  5. Reproductive Medicine & Infertility Associates, Woodbury, MN, USA

    D A Dumesic

  6. Cato Bio Ventures, Durham, NC, USA

    J R Eisner

  7. Department of Medicine, Mayo Clinic, Rochester, MN, USA

    M D Jensen

  8. Department of Ob/Gyn, University of Wisconsin, Madison, WI, USA

    D A Dumesic, L D Whigham & D H Abbott

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  1. C M Bruns
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Correspondence to D H Abbott.

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Bruns, C., Baum, S., Colman, R. et al. Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome. Int J Obes 31, 1579–1585 (2007). https://doi.org/10.1038/sj.ijo.0803638

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