Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and physiological responses to maternal high-fat diet feeding.
Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and physiological responses to maternal high-fat diet feeding.
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DOI：
10.1210/en.2014-1131
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发表时间：
2014-06
期刊：
影响因子：
4.8
通讯作者：
Balthasar N
中科院分区：
文献类型：
--
作者：
Dearden L;Balthasar N
大量的动物和人类研究表明，早期生活环境显着影响成年代谢平衡，但后代代谢程序错误的病因仍然不完全清楚。在这里，我们确定了母体饮食本身对小鼠代谢健康和下丘脑转录组调控中后代性别特异性结果的影响。此外，为了定义母体饮食错误编程后代代谢平衡方面的发育期，我们调查了妊娠期和/或哺乳期母体高脂/高糖饮食喂养的后代生理和转录组学后果。我们证明，高脂肪/高糖饮食喂养的母鼠的雌性后代特别容易受到代谢紊乱与体重增加，由于产后过程，而在子宫内的影响的饮食最终导致葡萄糖稳态失调。此外，室旁下丘脑中葡萄糖和母亲饮食敏感的基因表达调节具有显著的性别二态性。总之，我们发现了女性特异性，母体饮食介导的在子宫内的后代葡萄糖稳态的错误编程和葡萄糖和母体饮食敏感的室旁下丘脑基因表达调节的显着性二态性。值得注意的是，雌性后代对母体高脂肪/高糖饮食的代谢脆弱性会在后代中传播肥胖和2型糖尿病的恶性循环。
A wealth of animal and human studies demonstrate that early life environment significantly influences adult metabolic balance, however the etiology for offspring metabolic misprogramming remains incompletely understood. Here, we determine the effect of maternal diet per se on offspring sex-specific outcomes in metabolic health and hypothalamic transcriptome regulation in mice. Furthermore, to define developmental periods of maternal diet misprogramming aspects of offspring metabolic balance, we investigated offspring physiological and transcriptomic consequences of maternal high-fat/high-sugar diet feeding during pregnancy and/or lactation. We demonstrate that female offspring of high-fat/high-sugar diet-fed dams are particularly vulnerable to metabolic perturbation with body weight increases due to postnatal processes, whereas in utero effects of the diet ultimately lead to glucose homeostasis dysregulation. Furthermore, glucose- and maternal-diet sensitive gene expression modulation in the paraventricular hypothalamus is strikingly sexually dimorphic. In summary, we uncover female-specific, maternal diet-mediated in utero misprogramming of offspring glucose homeostasis and a striking sexual dimorphism in glucose- and maternal diet-sensitive paraventricular hypothalamus gene expression adjustment. Notably, female offspring metabolic vulnerability to maternal high-fat/high-sugar diet propagates a vicious cycle of obesity and type 2 diabetes in subsequent generations.
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影响因子：
4.2
作者：
Fahrenkrog, S;Harder, T;Plagemann, A
通讯作者：
Plagemann, A
影响因子：
5.5
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Matthews, Phillippa A.;Samuelsson, Anne-Maj;Taylor, Paul D.
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Taylor, Paul D.
影响因子：
56.9
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Bouret, SG;Draper, SJ;Simerly, RB
通讯作者：
Simerly, RB
影响因子：
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Oben, Jude A.;Mouralidarane, Angelina;Taylor, Paul D.
通讯作者：
Taylor, Paul D.
影响因子：
30.8
作者：
Loos, Ruth J. F.;Lindgren, Cecilia M.;Li, Shengxu;Wheeler, Eleanor;Zhao, Jing Hua;Prokopenko, Inga;Inouye, Michael;Freathy, Rachel M.;Attwood, Antony P.;Beckmann, Jacques S.;Berndt, Sonja I.;Bergmann, Sven;Bennett, Amanda J.;Bingham, Sheila A.;Bochud, Murielle;Brown, Morris;Cauchi, Stephane;Connell, John M.;Cooper, Cyrus;Smith, George Davey;Day, Ian;Dina, Christian;De, Subhajyoti;Dermitzakis, Emmanouil T.;Doney, Alex S. F.;Elliott, Katherine S.;Elliott, Paul;Evans, David M.;Farooqi, I. Sadaf;Froguel, Philippe;Ghori, Jilur;Groves, Christopher J.;Gwilliam, Rhian;Hadley, David;Hall, Alistair S.;Hattersley, Andrew T.;Hebebrand, Johannes;Heid, Iris M.;Herrera, Blanca;Hinney, Anke;Hunt, Sarah E.;Jarvelin, Marjo-Riitta;Johnson, Toby;Jolley, Jennifer D. M.;Karpe, Fredrik;Keniry, Andrew;Khaw, Kay-Tee;Luben, Robert N.;Mangino, Massimo;Marchini, Jonathan;McArdle, Wendy L.;McGinnis, Ralph;Meyre, David;Munroe, Patricia B.;Morris, Andrew D.;Ness, Andrew R.;Neville, Matthew J.;Nica, Alexandra C.;Ong, Ken K.;O'Rahilly, Stephen;Owen, Katharine R.;Palmer, Colin N. A.;Papadakis, Konstantinos;Potter, Simon;Pouta, Anneli;Qi, Lu;Randall, Joshua C.;Rayner, Nigel W.;Ring, Susan M.;Sandhu, Manjinder S.;Scherag, Andre;Sims, Matthew A.;Song, Kijoung;Soranzo, Nicole;Speliotes, Elizabeth K.;Syddall, Holly E.;Teichmann, Sarah A.;Timpson, Nicholas J.;Tobias, Jonathan H.;Uda, Manuela;Vogel, Carla I. Ganz;Wallace, Chris;Waterworth, Dawn M.;Weedon, Michael N.;Willer, Cristen J.;Wraight, Vicki L.;Yuan, Xin;Zeggini, Eleftheria;Hirschhorn, Joel N.;Strachan, David P.;Ouwehand, Willem H.;Caulfield, Mark J.;Samani, Nilesh J.;Frayling, Timothy M.;Vollenweider, Peter;Waeber, Gerard;Mooser, Vincent;Deloukas, Panos;McCarthy, Mark I.;Wareham, Nicholas J.;Barroso, Ines
通讯作者：
Barroso, Ines