Title: | Aromatase-deficient (ArKO) mice accumulate excess adipose tissue |
Author(s): | Jones ME; Thorburn AW; Britt KL; Hewitt KN; Misso ML; Wreford NG; Proietto J; Oz OK; Leury BJ; Robertson KM; Yao S; Simpson ER; |
Address: | "Prince Henry's Institute of Medical Research, P.O. Box 5152, Vic. 3168, Clayton, Australia. margaret.jones@med.monash.edu.au" |
Journal Title: | J Steroid Biochem Mol Biol |
DOI: | 10.1016/s0960-0760(01)00136-4 |
ISSN/ISBN: | 0960-0760 (Print) 0960-0760 (Linking) |
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: | Adipose Tissue/*enzymology/metabolism/*pathology Animals Aromatase/*deficiency/genetics/physiology Blood Glucose/metabolism Body Composition Body Weight Cell Count Cholesterol/blood Energy Metabolism Estrogens/biosynthesis/deficiency Fatty Liver/genetics/; |
Notes: | "MedlineJones, M 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 eng R37-AG08174/AG/NIA NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 2002/02/19 J Steroid Biochem Mol Biol. 2001 Dec; 79(1-5):3-9. doi: 10.1016/s0960-0760(01)00136-4" |