Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/80548
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Type: Journal article
Title: Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring
Author: Nicholas, L.
Rattanatray, L.
MacLaughlin, S.
Ozanne, S.
Kleemann, D.
Walker, S.
Morrison, J.
Zhang, S.
Muhlhausler, B.
Martin-Gronert, M.
McMillen, I.
Citation: The FASEB Journal, 2013; 27(9):3786-3796
Publisher: Federation of American Societies for Experimental Biology
Issue Date: 2013
ISSN: 1530-6860
1530-6860
Statement of
Responsibility: 
Lisa M. Nicholas, Leewen Rattanatray, Severence M. MacLaughlin, Susan E. Ozanne, Dave O. Kleemann, Simon K. Walker, Janna L. Morrison, Song Zhang, Beverley S. Muhlhäusler, Malgorzata S. Martin-Gronert, and Isabella C. McMillen
Abstract: Our aim was to determine the effect of exposure to maternal obesity or to maternal weight loss around conception on the programming of hepatic insulin signaling in the offspring. We used an embryo transfer model in sheep to investigate the effects of exposure to either maternal obesity or to weight loss in normal and obese mothers preceding and for 1 wk after conception on the expression of hepatic insulin-signaling and gluconeogenic factors and key miRNAs involved in insulin signaling in the offspring. We found that exposure to maternal obesity resulted in increased hepatic miR-29b (P<0.05), miR-103 (P<0.01), and miR-107 (P<0.05) expression, a decrease in IR (P<0.05), phopsho-Akt (P<0.01), and phospho-FoxO1 (P<0.01) abundance, and a paradoxical decrease in 11βHSD1 (P<0.05), PEPCK-C (P<0.01), and PEPCK-M (P<0.05) expression in lambs. These changes were ablated by a period of moderate dietary restriction imposed during the periconceptional period. Maternal dietary restriction alone also resulted in decreased abundance of a separate subset of hepatic insulin-signaling molecules, namely, IRS1 (P<0.05), PDK1 (P<0.01), phospho-PDK1 (P<0.05), and aPKCζ (P<0.05) and in decreased PEPCK-C (P<0.01) and G6Pase (P<0.01) expression in the lamb. Our findings highlight the sensitivity of the epigenome to maternal nutrition around conception and the need for dietary interventions that maximize metabolic benefits and minimize metabolic costs for the next generation.
Keywords: pregnancy; embryo; fetus; diabetes; programming; microRNAs
Rights: © FASEB
RMID: 0020131361
DOI: 10.1096/fj.13-227918
Appears in Collections:Molecular and Biomedical Science publications

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