Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity

The aromatase-knockout (ArKO) mouse provides a useful model to examine the role that estrogens play in development and homeostasis in mammals. Lacking a functional Cyp19 gene, which encodes aromatase, the ArKO mouse cannot sy nthesize endogenous estrogens. We examined the adipose depots of male and f emale ArKO mice, observing that these animals progressively accumulate sign ificantly more intraabdominal adipose tissue than their wild-type (WT) litt ermates, reflected in increased adipocyte volume at gonadal and infrarenal sites. This increased adiposity was not due to hyperphagia or reduced resti ng energy expenditure, but was associated with reduced spontaneous physical activity levels, reduced glucose oxidation, and a decrease in lean body ma ss. Elevated circulating levels of leptin and cholesterol were present in 1 -year-old ArKO mice compared with WT controls, as were elevated insulin lev els, although blood glucose levels were unchanged. Associated with these ch anges, a striking accumulation of lipid droplets was observed in the livers of ArKO animals. Our findings demonstrate an important role for estrogen i n the maintenance of lipid homeostasis in both males and females.