Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle

被引:14
作者
Alexanderson, Camilla [1 ]
Eriksson, Elias [2 ]
Stener-Victorin, Elisabet [1 ]
Lonn, Malin [3 ]
Holmang, Agneta [1 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, SE-40530 Gothenburg, Sweden
[2] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Pharmacol, SE-40530 Gothenburg, Sweden
[3] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab, SE-40530 Gothenburg, Sweden
基金
英国医学研究理事会;
关键词
ACYLATION-STIMULATING PROTEIN; VISCERAL ADIPOSE-TISSUE; DEPENDENT DIABETES-MELLITUS; PPAR-DELTA AGONIST; GROWTH-FACTOR-BETA; GENE-EXPRESSION; UNCOUPLING PROTEIN-3; GLUCOSE-TRANSPORT; ANDROGEN EXCESS; TNF-ALPHA;
D O I
10.1677/JOE-08-0534
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 analysed 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. 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 beta 1 (Tgf beta 1). C3 and MCP-1 are both related to insulin resistance, and C3, MCP-1 and TGF beta 1 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 s.c. inguinal adipose tissue, expression of Tgf beta 1, Ppard and C3 was decreased, while expression of Rpb4 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. journal of Endocrinology (2009) 201, 49-58
引用
收藏
页码:49 / 58
页数:10
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