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

94 Citations (Scopus)

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 - 2001

Fingerprint

Aromatase
Knockout Mice
Adipose Tissue
Tissue
Estrogens
Animals
Lipids
Hyperphagia
Intra-Abdominal Fat
Adiposity
Leptin
Adipocytes
Liver
Energy Metabolism
Blood Glucose
Homeostasis
Genes
Steroids
Cholesterol
Maintenance

Keywords

  • Aromatse
  • Cholesterol
  • Estrogen deficiency
  • Insulin
  • Leptin

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Jones, M. E. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Misso, M. L., Wreford, N. G., ... 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

Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. / Jones, Margaret E E; Thorburn, Anne W.; Britt, Kara L.; Hewitt, Kylie N.; Misso, Marie L.; Wreford, Nigel G.; Proietto, Joseph; Oz, Orhan K.; Leury, Brian J.; Robertson, Kirsten M.; Yao, Shenggen; Simpson, Evan R.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 79, No. 1-5, 2001, p. 3-9.

Research output: Contribution to journalArticle

Jones, MEE, Thorburn, AW, Britt, KL, Hewitt, KN, Misso, ML, Wreford, NG, Proietto, J, Oz, OK, Leury, BJ, Robertson, KM, Yao, S & Simpson, ER 2001, 'Aromatase-deficient (ArKO) mice accumulate excess adipose tissue', Journal of Steroid Biochemistry and Molecular Biology, vol. 79, no. 1-5, pp. 3-9. https://doi.org/10.1016/S0960-0760(01)00136-4
Jones, Margaret E E ; Thorburn, Anne W. ; Britt, Kara L. ; Hewitt, Kylie N. ; Misso, Marie L. ; Wreford, Nigel G. ; Proietto, Joseph ; Oz, Orhan K. ; Leury, Brian J. ; Robertson, Kirsten M. ; Yao, Shenggen ; Simpson, Evan R. / Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. In: Journal of Steroid Biochemistry and Molecular Biology. 2001 ; Vol. 79, No. 1-5. pp. 3-9.
@article{70ca0ca857dc4fe98fad8f17a158a7d9,
title = "Aromatase-deficient (ArKO) mice accumulate excess adipose tissue",
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.",
keywords = "Aromatse, Cholesterol, Estrogen deficiency, Insulin, Leptin",
author = "Jones, {Margaret E E} and Thorburn, {Anne W.} and Britt, {Kara L.} and Hewitt, {Kylie N.} and Misso, {Marie L.} and Wreford, {Nigel G.} and Joseph Proietto and Oz, {Orhan K.} and Leury, {Brian J.} and Robertson, {Kirsten M.} and Shenggen Yao and Simpson, {Evan R.}",
year = "2001",
doi = "10.1016/S0960-0760(01)00136-4",
language = "English (US)",
volume = "79",
pages = "3--9",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",
number = "1-5",

}

TY - JOUR

T1 - Aromatase-deficient (ArKO) mice accumulate excess adipose tissue

AU - Jones, Margaret E E

AU - Thorburn, Anne W.

AU - Britt, Kara L.

AU - Hewitt, Kylie N.

AU - Misso, Marie L.

AU - Wreford, Nigel G.

AU - Proietto, Joseph

AU - Oz, Orhan K.

AU - Leury, Brian J.

AU - Robertson, Kirsten M.

AU - Yao, Shenggen

AU - Simpson, Evan R.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Aromatse

KW - Cholesterol

KW - Estrogen deficiency

KW - Insulin

KW - Leptin

UR - http://www.scopus.com/inward/record.url?scp=0035716557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035716557&partnerID=8YFLogxK

U2 - 10.1016/S0960-0760(01)00136-4

DO - 10.1016/S0960-0760(01)00136-4

M3 - Article

C2 - 11850201

AN - SCOPUS:0035716557

VL - 79

SP - 3

EP - 9

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 1-5

ER -