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Diabetologia
Published in: Diabetologia 9/2011

01-09-2011 | Article

Novel hormone-regulated genes in visceral adipose tissue: cloning and identification of proinflammatory cytokine-like mouse and human MEDA-7: implications for obesity, insulin resistance and the metabolic syndrome

Authors: H. Zhang, X. Chen, M. R. Sairam

Published in: Diabetologia | Issue 9/2011

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Abstract

Aims/hypothesis

We sought to characterise novel genes dysregulated by sex hormonal imbalances that induce obesity and metabolic disorder in a setting of oestrogen deficiency and androgen dominance in follicle-stimulating hormone receptor (For [also known as Fshr]) knockout female mice.

Methods

Transcriptome analysis of mesenteric adipose tissue (MAT) of mutants revealed novel genes. One novel gene named Meda-7 was selected for study. Meda-7 was cloned from mouse and human adipose tissue; its expression, hormonal regulation and function were characterised.

Results

Mouse Meda-7 is richly expressed in deep visceral adipose tissue and encodes a 22 kDa secreted protein with 71% homology to human mesenteric oestrogen-dependent adipose gene- 7 (MEDA-7) protein. Both have six conserved cysteines like many cytokines. In obese patients, MEDA-7 is more abundant in omental than subcutaneous fat. Meda-7 is downregulated in For-knockout female MAT at 5 months (obese state) followed by steep upregulation at 9 months (prediabetic condition) when mutants progress towards the metabolic syndrome. Meda-7 is expressed predominantly in the stromal–vascular cell fraction. In this fraction,M1-proinflammatorymacrophages are rich in Meda-7. Meda-7 dysregulation in 5-month-old For-knockout MAT is restored by oestrogen, but treatment has no effect in older mutants. Overabundance of MEDA-7 in HEK-293 cells enhances cell proliferation via p42/44 mitogen-activated protein kinases. Secreted MEDA-7 attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes, while downregulating glucose transporter-4 and upregulating both monocyte chemotactic protein-1 and suppressor of cytokine signalling-3. Downstream activity of the insulin signalling mediator, phospho-AKT, is also downregulated.

Conclusions/interpretation

MEDA-7 is a hormone-regulated adipokine/proinflammatory cytokine that is implicated in causing chronic inflammation, affecting cellular expansion and blunting insulin response in adipocytes.
Appendix
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Metadata
Title
Novel hormone-regulated genes in visceral adipose tissue: cloning and identification of proinflammatory cytokine-like mouse and human MEDA-7: implications for obesity, insulin resistance and the metabolic syndrome
Authors
H. Zhang
X. Chen
M. R. Sairam
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 9/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2212-7

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