Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/82760
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Type: Journal article
Title: Differential effects of exposure to maternal obesity or maternal weight loss during the periconceptional period in the sheep on insulin signalling molecules in skeletal muscle of the offspring at 4 months of age
Author: Nicholas, L.
Morrison, J.
Rattanatray, L.
Ozanne, S.
Kleemann, D.
Walker, S.
MacLaughlin, S.
Zhang, S.
Martin-Gronert, M.
McMillen, I.
Citation: PLoS One, 2013; 8(12):1-11
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Lisa M. Nicholas, Janna L. Morrison, Leewen Rattanatray, Susan E. Ozanne, Dave O. Kleemann, Simon K. Walker, Severence M. MacLaughlin, Song Zhang, Malgorzata S. Martin-Gronert, Isabella C. McMillen
Abstract: Exposure to maternal obesity before and/or throughout pregnancy may increase the risk of obesity and insulin resistance in the offspring in childhood and adult life, therefore, resulting in its transmission into subsequent generations. We have previously shown that exposure to maternal obesity around the time of conception alone resulted in increased adiposity in female lambs. Changes in the abundance of insulin signalling molecules in skeletal muscle and adipose tissue precede the development of insulin resistance and type 2 diabetes. It is not clear, however, whether exposure to maternal obesity results in insulin resistance in her offspring as a consequence of the impact of increased adiposity on skeletal muscle or as a consequence of the programming of specific changes in the abundance of insulin signalling molecules in this tissue. We have used an embryo transfer model in the sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for one week after conception on the expression and abundance of insulin signalling molecules in muscle in the offspring. We found that exposure to maternal obesity resulted in lower muscle GLUT-4 and Ser 9 phospho-GSK3α and higher muscle GSK3α abundance in lambs when compared to lambs conceived in normally nourished ewes. Exposure to maternal weight loss in normal or obese mothers, however, resulted in lower muscle IRS1, PI3K, p110β, aPKCζ, Thr 642 phospho-AS160 and GLUT-4 abundance in the offspring. In conclusion, maternal obesity or weight loss around conception have each programmed specific changes on subsets of molecules in the insulin signalling, glucose transport and glycogen synthesis pathways in offspring. There is a need for a stronger evidence base to ensure that weight loss regimes in obese women seeking to become pregnant minimize the metabolic costs for the next generation.
Keywords: Muscle, Skeletal; Animals; Sheep; Prenatal Exposure Delayed Effects; Insulin Resistance; Obesity; Weight Loss; Insulin; Muscle Proteins; Signal Transduction; Fertilization; Pregnancy; Female
Description: Published online: December 26, 2013
Rights: © 2013 Nicholas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020134229
DOI: 10.1371/journal.pone.0084594
Grant ID: http://purl.org/au-research/grants/nhmrc/631928
Appears in Collections:Obstetrics and Gynaecology publications

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