Aromatase-deficient (ArKO) mice accumulate excess adipose tissue

Margaret E E Jones, Anne W. Thorburn, Kara L. Britt, Kylie N. Hewitt, Marie L. Misso, Nigel G. Wreford, Joseph Proietto, Orhan K. Oz, Brian J. Leury, Kirsten M. Robertson, Shenggen Yao, Evan R. Simpson

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Aromatase is the enzyme which catalyses the conversion of C19 steroids into C18 estrogens. We have generated a mouse model wherein the Cyp19 gene, which encodes aromatase, has been disrupted, and hence, the aromatase knockout (ArKO) mouse cannot synthesise endogenous estrogens. We examined the consequences of estrogen deficiency on accumulation of adipose depots in male and female ArKO mice, observing that these animals progressively accrue significantly more intra-abdominal adipose tissue than their wildtype (WT) litter mates, reflected in increased adipocyte volume and number. This increased adiposity was not due to hyperphagia or reduced resting energy expenditure, but was associated with reduced spontaneous physical activity levels, reduced glucose oxidation, and a decrease in lean body mass. Elevated circulating levels of leptin and cholesterol were present in 1-year-old ArKO mice compared to WT controls, as were elevated insulin levels, although blood glucose was unchanged. Associated with these changes, the livers of ArKO animals were characterised by a striking accumulation of lipid droplets. Our findings demonstrate an important role for estrogen in the maintenance of lipid homeostasis in both males and females.

Original languageEnglish (US)
Pages (from-to)3-9
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume79
Issue number1-5
DOIs
StatePublished - Dec 1 2001

Keywords

  • Aromatse
  • Cholesterol
  • Estrogen deficiency
  • Insulin
  • Leptin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Jones, M. E. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Misso, M. L., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., & Simpson, E. R. (2001). Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. Journal of Steroid Biochemistry and Molecular Biology, 79(1-5), 3-9. https://doi.org/10.1016/S0960-0760(01)00136-4