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

TLDR

The aromatase‑knockout (ArKO) mouse, lacking the Cyp19 gene and endogenous estrogens, serves as a model to study estrogen’s role in mammalian development and homeostasis. The study compared intraabdominal adipose depots of male and female ArKO mice to wild‑type littermates, finding progressive accumulation of larger adipocytes in gonadal and infrarenal sites. ArKO mice exhibit increased intraabdominal adiposity without hyperphagia or lowered energy expenditure, accompanied by reduced physical activity, lower glucose oxidation, decreased lean mass, elevated leptin, cholesterol, and insulin, hepatic lipid droplet accumulation, and these findings underscore estrogen’s essential role in lipid homeostasis in both sexes.

Abstract

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 synthesize endogenous estrogens. We examined the adipose depots of male and female ArKO mice, observing that these animals progressively accumulate significantly more intraabdominal adipose tissue than their wild-type (WT) littermates, reflected in increased adipocyte volume at gonadal and infrarenal sites. 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 with WT controls, as were elevated insulin levels, although blood glucose levels were unchanged. Associated with these changes, a striking accumulation of lipid droplets was observed in the livers of ArKO animals. Our findings demonstrate an important role for estrogen in the maintenance of lipid homeostasis in both males and females.