This is just the "bookmarking" blog where I will post only links and perhaps abstracts I've come across that are of interest to me and may someday be discussed in a blog post.

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Wednesday, February 15, 2012

Cellular and Molecular Characterization of the Adipose Phenotype of the Aromatase-Deficient Mouse

Cellular and Molecular Characterization of the Adipose Phenotype of the Aromatase-Deficient Mouse

Estrogen deficiency in the aromatase knockout (ArKO) mouse leads to the development of obesity by as early as 3 months of age, which is characterized by a marked increase in the weights of gonadal and infrarenal fat pads. Humans with natural mutations of the aromatase gene also develop a metabolic syndrome. In the present study cellular and molecular parameters were investigated in gonadal adipose tissue from 10-wk-old wild-type (WT) and ArKO female mice treated with 17β-estradiol or placebo to identify the basis for the increase in intraabdominal obesity. Stereological examination revealed that adipocytes isolated from ArKO mice were significantly larger and more abundant than adipocytes isolated from WT mice. Upon treatment with estrogen, the volume of these adipocytes was greatly reduced, whereas the reduction in the number of adipocytes was much less pronounced. Transcriptional analysis using real-time PCR revealed concomitant changes with adipocyte volume in the levels of transcripts encoding leptin and lipoprotein lipase, whereas peroxisome proliferator-activated receptor γ levels followed a pattern closer to that of adipocyte number. Little change was observed in levels of transcripts for factors involved in de novo fatty acid synthesis, β-oxidation, and lipolysis, suggesting that changes in the uptake of lipids from the circulation are the main mechanisms by which estrogen regulates lipid metabolism in these mice.

Elevated Free Fatty Acids Impair Glucose Metabolism in Women

Elevated Free Fatty Acids Impair Glucose Metabolism in Women

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

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 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.