Molecular Metabolism ( IF 7.0 ) Pub Date : 2020-02-15 , DOI: 10.1016/j.molmet.2020.02.006 Roberta Haddad-Tóvolli 1 , Jordi Altirriba 2 , Arnaud Obri 1 , Elena Eyre Sánchez 1 , Iñigo Chivite 1 , Maria Milà-Guasch 1 , Sara Ramírez 1 , Alicia G Gómez-Valadés 1 , Macarena Pozo 1 , Jasmine Burguet 3 , Licio A Velloso 4 , Marc Claret 5
|
Objective
Maternal unbalanced nutritional habits during embryonic development and perinatal stages perturb hypothalamic neuronal programming of the offspring, thus increasing obesity-associated diabetes risk. However, the underlying molecular mechanisms remain largely unknown. In this study we sought to determine the translatomic signatures associated with pro-opiomelanocortin (POMC) neuron malprogramming in maternal obesogenic conditions.
Methods
We used the RiboTag mouse model to specifically profile the translatome of POMC neurons during neonatal (P0) and perinatal (P21) life and its neuroanatomical, functional, and physiological consequences.
Results
Maternal high-fat diet (HFD) exposure did not interfere with offspring's hypothalamic POMC neuron specification, but significantly impaired their spatial distribution and axonal extension to target areas. Importantly, we established POMC neuron-specific translatome signatures accounting for aberrant neuronal development and axonal growth. These anatomical and molecular alterations caused metabolic dysfunction in early life and adulthood.
Conclusions
Our study provides fundamental insights on the molecular mechanisms underlying POMC neuron malprogramming in obesogenic contexts.
中文翻译：
阿黑皮质素原 (POMC) 神经元翻译组特征是小鼠肥胖妊娠期程序异常的基础。
客观的
胚胎发育和围产期阶段母亲不平衡的营养习惯会扰乱后代的下丘脑神经元编程，从而增加与肥胖相关的糖尿病风险。然而，潜在的分子机制仍然很大程度上未知。在这项研究中，我们试图确定与产妇肥胖条件下阿片黑皮素原（POMC）神经元编程错误相关的翻译标记。
方法
我们使用 RiboTag 小鼠模型来专门分析新生儿 (P0) 和围产期 (P21) 生命期间 POMC 神经元的翻译组及其神经解剖学、功能和生理学后果。
结果
母亲的高脂肪饮食（HFD）暴露不会干扰后代下丘脑 POMC 神经元的规范，但会显着损害其空间分布和轴突向目标区域的延伸。重要的是，我们建立了 POMC 神经元特异性翻译组特征，解释了异常的神经元发育和轴突生长。这些解剖学和分子学的改变导致了生命早期和成年期的代谢功能障碍。
结论
我们的研究提供了关于肥胖背景下 POMC 神经元编程错误的分子机制的基本见解。
京公网安备 11010802027423号