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Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice.

Journal article
Authors Claes Ohlsson
Ann Hammarstedt
Liesbeth Vandenput
Niina Saarinen
Henrik Ryberg
Sara H Windahl
Helen H. Farman
John-Olov Jansson
Sofia Movérare-Skrtic
Ulf Smith
Fu-Ping Zhang
Matti Poutanen
Shahram Hedjazifar
Klara Sjögren
Published in American journal of physiology. Endocrinology and metabolism
Volume 313
Issue 4
Pages E450-E462
ISSN 1522-1555
Publication year 2017
Published at Institute of Neuroscience and Physiology
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages E450-E462
Language en
Subject categories Other Medical Sciences


Females are in general more insulin sensitive than males. To investigate if this is a direct effect of sex-steroids (SS) in white adipose tissue (WAT), we developed a male mouse model over expressing the aromatase enzyme, converting testosterone (T) to estradiol (E2), specifically in WAT (Ap2-arom mice). Adipose tissue E2 levels were increased while circulating SS levels were unaffected in male Ap2-arom mice. Importantly, male Ap2-arom mice were more insulin sensitive compared with WT mice and exhibited increased serum adiponectin levels and upregulated expression of Glut4 and Irs1 in WAT. The expression of markers of macrophages and immune cell infiltration was markedly decreased in WAT of male Ap2-arom mice. The adipogenesis was enhanced in male Ap2-arom mice, supported by elevated Pparg expression in WAT and enhanced differentiation of pre-adipocyte into mature adipocytes. In summary, increased adipose tissue aromatase activity reduces adipose tissue inflammation and improves insulin sensitivity in male mice. We propose that estrogen increases insulin sensitivity via a local effect in WAT on adiponectin expression, adipose tissue inflammation, and adipogenesis.

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