Maternal high fat diet exposure is associated with increased hepcidin levels, decreased myelination, and neurobehavioral changes in male offspring.
Maternal high fat diet exposure is associated with increased hepcidin levels, decreased myelination, and neurobehavioral changes in male offspring.
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DOI：
10.1016/j.bbi.2016.08.005
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Rogers LK
中科院分区：
文献类型：
--
作者：
Graf AE;Lallier SW;Waidyaratne G;Thompson MD;Tipple TE;Hester ME;Trask AJ;Rogers LK
母体肥胖会引发慢性炎症反应，这种反应在围产期会影响胎儿/新生儿。炎症、铁调节和髓鞘形成密切相关，这些过程的紊乱可能对神经发育产生有害影响。炎症会使铁调素水平升高，进而导致铁转运蛋白减少以及髓鞘形成所需的可用铁减少。我们目前的研究旨在验证以下假设：1）怀孕前及怀孕期间母体的高脂肪饮食（HFD）足以引发炎症并改变后代大脑中的铁调节；2）高脂肪饮食暴露与后代髓鞘形成改变和神经行为缺陷有关。我们的数据显示，与喂食对照饮食（CD）的母鼠相比，怀孕前喂食高脂肪饮食的母鼠血清中的炎症细胞因子有适度增加。在出生后第7天（PN7）观察到白细胞介素 - 5（IL - 5）早期升高和白细胞介素 - 10（IL - 10）降低，而高脂肪饮食暴露的幼崽在出生后第21天（PN21）白细胞介素 - 5仍保持升高。在出生时（PN0），高脂肪饮食母鼠所生幼崽的全脑匀浆中大多数细胞因子水平较高，但在出生后第21天与对照饮食母鼠所生幼崽相比无差异或更低。相反，炎症介导的转录因子Nurr77在出生后第21天仍保持升高。出生时，高脂肪饮食母鼠所生幼崽的大脑铁调素、铁转运蛋白和L - 铁蛋白水平高于对照饮食母鼠所生幼崽。铁调素水平在出生后第7天和第21天仍保持升高，而铁转运蛋白和L - 铁蛋白水平在出生后第7天较低，在出生后第21天无差异。在出生后第21天，母体高脂肪饮食母鼠所生的雄性幼崽内侧皮质的髓鞘形成减少，但雌性幼崽未出现这种情况。这些结构变化仅与雄性幼崽在4个月时的行为（新物体识别）变化相关。我们的数据表明，母体肥胖（高脂肪饮食）会导致后代大脑中铁调节紊乱，并使雄性幼崽出现结构和神经行为缺陷。
Maternal obesity induces chronic inflammatory responses that impact the fetus/neonate during the perinatal period. Inflammation, iron regulation, and myelination are closely interconnected and disruptions in these processes may have deleterious effects on neurodevelopment. Hepcidin levels are increased in response to inflammation causing subsequent decreases in ferroportin and available iron needed for myelination. Our current studies were designed to test the hypotheses that: 1) maternal high fat diet (HFD) prior to and during pregnancy is sufficient to induce inflammation and alter iron regulation in the brain of the offspring, and 2) HFD exposure is associated with altered myelination and neurobehavioral deficits in the offspring. Our data revealed modest increases in inflammatory cytokines in the serum of dams fed HFD prior to pregnancy compared to dams fed a control diet (CD). Early increases in IL-5 and decreases in IL-10 were observed in serum at PN7 while IL-5 remained elevated at PN21 in the HFDexposed pups. At PN0, most cytokine levels in whole brain homogenates were higher in the pups born to HFD-fed dams but were not different or were lower than in pups born to CD-fed dams at PN21. Conversely, the inflammation mediated transcription factor Nurr77 remained elevated at PN21. At birth, brain hepcidin, ferroportin, and l-ferritin levels were elevated in pups born to HFD-fed dams compared to pups born to CD-fed dams. Hepcidin levels remained elevated at PN7 and PN21 while ferroportin and l-ferritin levels were lower at PN7 and were not different at PN21. Decreases in myelination in the medial cortex were observed in male but not in female pups born to maternal HFD-fed dams at PN21. These structural changes correlated with changes in behavior (novel object recognition) in at 4 months in males only. Our data indicate that maternal obesity (HFD) results in disruption of iron regulation in the brains of the offspring with structural and neurobehavioral deficits in males.
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影响因子：
3.3
作者：
Pistell PJ;Morrison CD;Gupta S;Knight AG;Keller JN;Ingram DK;Bruce-Keller AJ
通讯作者：
Bruce-Keller AJ
影响因子：
2.9
作者：
Reynolds, L. C.;Inder, T. E.;Neil, J. J.;Pineda, R. G.;Rogers, C. E.
通讯作者：
Rogers, C. E.
影响因子：
4.3
作者：
Rivera HM;Christiansen KJ;Sullivan EL
通讯作者：
Sullivan EL
影响因子：
8
作者：
Boney, CM;Verma, A;Vohr, BR
通讯作者：
Vohr, BR
影响因子：
4.6
作者：
Mandillo, Silvia;Tucci, Valter;Wurst, Wolfgang
通讯作者：
Wurst, Wolfgang