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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0534v1 201/1/49    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Alexanderson, C. Articles by Holmäng, A. Search for Related Content PubMed PubMed Citation Articles by Alexanderson, C. Articles by Holmäng, A.

C Alexanderson, Göteborg, 405 30, Sweden
E Eriksson, Institute for Neuroscience & Physiology, Gothenburg University, Gothenburg, Sweden
E Stener-Victorin, Institute for Neuroscience & Physiology, Gothenburg University, Gothenburg, Sweden
M Lönn, Institute for Medicine, Gothenburg University, Gothenburg, Sweden
A Holmäng, Institute for Neuroscience & Physiology, Gothenburg University, Gothenburg, Sweden

Correspondence: Camilla Alexanderson, Email: camilla.alexandersongbg{at}gmail.com

Abstract

Early postnatal events can predispose to metabolic and endocrine disease in adulthood. In this study, we evaluated the programming effects of a single early postnatal oestradiol injection on insulin sensitivity in adult female rats. We also assessed the expression of genes involved in inflammation and glucose metabolism in skeletal muscle and adipose tissue and analyzed circulating inflammation markers as possible mediators of insulin resistance. Neonatal oestradiol exposure reduced insulin sensitivity and increased plasma levels of monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 (sICAM-1). In skeletal muscle, oestradiol increased the expression of genes encoding complement component 3 (C3), Mcp-1, retinol binding protein-4 (Rbp4), and transforming growth factor beta1 (Tgfb1). C3 and MCP-1 are both related to insulin resistance, and C3, MCP-1 and TGFb1 are also involved in inflammation. Expression of genes encoding glucose transporter-4 (Glut 4), carnitine-palmitoyl transferase 1b (Cpt1b), peroxisome proliferator-activated receptor delta (Ppard), and uncoupling protein 3 (Ucp3), which are connected to glucose uptake, lipid oxidation, and energy uncoupling, was down regulated. Expression of several inflammatory genes in skeletal muscle correlated negatively with whole-body insulin sensitivity. In subcutaneous inguinal adipose tissue, expression of Tgfb1, Ppard, and C3 was decreased, while expression of Rbp4 and Cpt1b was increased. Inguinal adipose tissue weight was increased but adipocyte size was unaltered, suggesting an increased number of adipocytes. We suggest that early neonatal oestrogen exposure may reduce insulin sensitivity by inducing chronic, low-grade systemic and skeletal muscle inflammation and disturbances of glucose and lipid metabolism in skeletal muscle in adulthood.