PMID- 24773340
OWN - NLM
STAT- MEDLINE
DCOM- 20140825
LR  - 20171116
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 155
IP  - 7
DP  - 2014 Jul
TI  - Maternal obesity and IL-6 lead to aberrant developmental gene expression and 
      deregulated neurite growth in the fetal arcuate nucleus.
PG  - 2566-77
LID - 10.1210/en.2013-1968 [doi]
AB  - 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.
FAU - Sanders, Tessa R
AU  - Sanders TR
AD  - Centre for Neuroendocrinology, Gravida: National Research Centre for Growth and 
      Development, Department of Anatomy, University of Otago School of Medical 
      Sciences, Dunedin 9054, New Zealand.
FAU - Kim, Dong Won
AU  - Kim DW
FAU - Glendining, Kelly A
AU  - Glendining KA
FAU - Jasoni, Christine L
AU  - Jasoni CL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140428
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Interleukin-6)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuropeptide Y)
RN  - 0 (Ntn1 protein, mouse)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 158651-98-0 (Netrin-1)
SB  - IM
MH  - Animals
MH  - Arcuate Nucleus of Hypothalamus/*drug effects/embryology/metabolism
MH  - Cells, Cultured
MH  - Diet, High-Fat/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Interleukin-6/blood/*pharmacology
MH  - Mice, Inbred C57BL
MH  - Nerve Growth Factors/genetics/metabolism
MH  - Netrin-1
MH  - Neurites/*drug effects/metabolism/physiology
MH  - Neuropeptide Y/genetics/metabolism
MH  - Obesity/etiology/genetics/*metabolism
MH  - Paraventricular Hypothalamic Nucleus/drug effects/embryology/metabolism
MH  - Pregnancy
MH  - Pregnancy Complications
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Suppressor Proteins/genetics/metabolism
EDAT- 2014/04/30 06:00
MHDA- 2014/08/26 06:00
CRDT- 2014/04/30 06:00
PHST- 2014/04/30 06:00 [entrez]
PHST- 2014/04/30 06:00 [pubmed]
PHST- 2014/08/26 06:00 [medline]
AID - 10.1210/en.2013-1968 [doi]
PST - ppublish
SO  - Endocrinology. 2014 Jul;155(7):2566-77. doi: 10.1210/en.2013-1968. Epub 2014 Apr 
      28.