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In order to investigate the possible involvement of endoplasmic reticulum (ER) stress in the developmental origins of hepatic steatosis associated with undernourishment in utero, we herein employed a fetal undernourishment mouse model by maternal caloric restriction in three cohorts; cohort 1) assessment of hepatic steatosis and the ER stress response at 9 weeks of age (wks) before a high fat diet (HFD), cohort 2) assessment of hepatic steatosis and the ER stress response on a HFD at 17 wks, cohort 3) assessment of hepatic steatosis and the ER stress response at 22 wks on a HFD after the alleviation of ER stress with a chemical chaperone, tauroursodeoxycholic acid (TUDCA), from 17 wks to 22 wks. Undernourishment in utero significantly deteriorated hepatic steatosis and led to the significant integration of the ER stress response on a HFD at 17 wks. The alleviation of ER stress by the TUDCA treatment significantly improved the parameters of hepatic steatosis in pups with undernourishment in utero, but not in those with normal nourishment in utero at 22 wks. These results suggest the pivotal involvement of the integration of ER stress in the developmental origins of hepatic steatosis in association with undernourishment in utero.

Undernourishment in utero Primes Hepatic Steatosis in Adult Mice Offspring on an Obesogenic Diet; Involvement of Endoplasmic Reticulum Stress.

作者信息

Muramatsu-Kato Keiko, Itoh Hiroaki, Kohmura-Kobayashi Yukiko, Ferdous Urmi J, Tamura Naoaki, Yaguchi Chizuko, Uchida Toshiyuki, Suzuki Kazunao, Hashimoto Koshi, Suganami Takayoshi, Ogawa Yoshihiro, Kanayama Naohiro

机构信息

Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu 431-3192 Japan.

Department of Preemptive Medicine and Metabolism, Tokyo 113-8510, Japan.

出版信息

Sci Rep. 2015 Nov 19;5:16867. doi: 10.1038/srep16867.

为了研究内质网（ER）应激是否可能参与子宫内营养不良相关的肝脂肪变性的发育起源，我们在此通过对三个队列的母鼠进行热量限制，采用了胎儿营养不良小鼠模型；队列1）在高脂饮食（HFD）前9周龄（wks）时评估肝脂肪变性和ER应激反应，队列2）在17周龄时评估HFD上的肝脂肪变性和ER应激反应，队列3）在17至22周龄期间用化学伴侣牛磺熊去氧胆酸（TUDCA）缓解ER应激后，在22周龄时评估HFD上的肝脂肪变性和ER应激反应。子宫内营养不良显著恶化了肝脂肪变性，并导致17周龄时HFD上ER应激反应的显著整合。TUDCA治疗缓解ER应激显著改善了子宫内营养不良幼崽的肝脂肪变性参数，但对22周龄时子宫内营养正常的幼崽没有改善作用。这些结果表明，ER应激的整合在子宫内营养不良相关的肝脂肪变性的发育起源中起关键作用。