Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring

作者：Nicholas Lisa M; Rattanatray Leewen; MacLaughlin Severence M; Ozanne Susan E; Kleemann Dave O; Walker Simon K; Morrison Janna L; Zhang Song; Muhlhaeusler Beverley S; Martin Gronert Malgorzata S; McMillen Isabella C^*

来源：The FASEB Journal, 2013, 27(9): 3786-3796.

DOI：10.1096/fj.13-227918

• pregnancy
• embryo
• fetus
• diabetes
• programming
• microRNAs

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%26lt;0.05), miR-103 (P%26lt;0.01), and miR-107 (P%26lt;0.05) expression, a decrease in IR (P%26lt;0.05), phopsho-Akt (P%26lt;0.01), and phospho-FoxO1 (P%26lt;0.01) abundance, and a paradoxical decrease in 11HSD1 (P%26lt;0.05), PEPCK-C (P%26lt;0.01), and PEPCK-M (P%26lt;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%26lt;0.05), PDK1 (P%26lt;0.01), phospho-PDK1 (P%26lt;0.05), and aPKC (P%26lt;0.05) and in decreased PEPCK-C (P%26lt;0.01) and G6Pase (P%26lt;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.Nicholas, L. M., Rattanatray, L., MacLaughlin, S. M., Ozanne, S. E., Kleemann, D. O., Walker, S. K., Morrison, J. L., Zhang, S., Muhlhausler, B. S., Martin-Gronert, M. S., McMillen, I. C. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring.

• 出版日期2013-9