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Maternal obesity and IL-6 lead to aberrant developmental gene expression and deregulated neurite growth in the fetal arcuate nucleus.

Abstract：

:Maternal obesity during pregnancy increases the risk of obesity in the offspring. Several observations have pointed to a causative role for the proinflammatory cytokine IL-6, but whether it is present in the fetal circulation and how it acts on the developing fetus are unclear. We first observed that postnatal day 0 offspring from obese mothers had significantly reduced neuropeptide Y (NPY) innervation of the paraventricular nucleus (PVN) compared with that for offspring of normal-weight controls. Thus, the growth of NPY neurites from the arcuate nucleus (ARC) was impaired in the fetal brain by maternal obesity. The neurite growth regulator, Netrin-1, was expressed in the ARC and PVN and along the pathway between the two at gestational day (GD) 17.5 in normal animals, making it likely to be involved in the development of NPY ARC-PVN projections. In addition, the expression of Dcc and Unc5d, receptors for Netrin-1, were altered in the GD17.5 ARC in obese but not normal weight pregnancies. Thus, this important developmental pathway is perturbed by maternal obesity and may explain the defect in NPY innervation of the PVN that occurs in fetuses developing in obese mothers. To investigate whether IL-6 may play a role in these developmental changes, we found first that IL-6 was significantly elevated in the fetal and maternal circulation in pregnancies of obese mice compared with those of normal-weight mice. In addition, treatment of GD17.5 ARC tissue with IL-6 in vitro significantly reduced ARC neurite outgrowth and altered developmental gene expression similar to maternal obesity in vivo. These findings demonstrate that maternal obesity may alter the way in which fetal ARC NPY neurons respond to key developmental signals that regulate normal prenatal neural connectivity and suggest a causative role for elevated IL-6 in these changes.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Sanders TR,Kim DW,Glendining KA,Jasoni CL

doi

10.1210/en.2013-1968

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

2566-77

issue

eissn

0013-7227

issn

1945-7170

journal_volume

155

pub_type

杂志文章

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Maternal obesity and IL-6 lead to aberrant developmental gene expression and deregulated neurite growth in the fetal arcuate nucleus.