Maternal perinatal calorie restriction temporally regulates the hepatic autophagy and redox status in male rat.
Maternal perinatal calorie restriction temporally regulates the hepatic autophagy and redox status in male rat.
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DOI：
10.1016/j.freeradbiomed.2018.09.029
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发表时间：
2019-01
影响因子：
7.4
通讯作者：
Freije WA
中科院分区：
文献类型：
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作者：
Devarajan A;Rajasekaran NS;Valburg C;Ganapathy E;Bindra S;Freije WA
宫内生长受限（IUGR）导致成人肥胖、心血管疾病和非酒精性脂肪性肝病/脂肪性肝炎。动物模型表明，宫内和产后早期热量限制（IPCR）相结合，改善这些后遗症在成年生活。IPCR预防成人发病的机制尚不清楚。自噬是一种溶酶体降解过程，可清除细胞成分并清除受损的细胞器、蛋白质和氧化剂。在这项研究中，我们假设IPCR可以调节雄性大鼠后代肝脏中的自噬。在雄性IUGR大鼠后代出生时（d1）和出生后第21天（p21），IPCR雄性大鼠后代在发育的所有三个阶段（起始、延长和成熟）的肝脏自噬显著减少。然而，在整个成年期接受正常饮食后，老年IPCR大鼠（生命第450天（p450））的肝脏自噬增加，与早期生活中观察到的情况形成直接对比。在d21减少的自噬导致泛素化蛋白和脂质氧化产物的积累，而在晚年增加的自噬具有相反的效果。氧化脂质在第1天IUGR治疗没有变化，表明在生命早期，自噬减少先于氧化应激。当检查调节自噬的细胞信号通路时，发现5′腺苷一磷酸激活的蛋白激酶通路（AMPK）而不是内质应激通路被改变，这表明在IPCR大鼠中自噬通过AMPK信号通路调节。总之，这项研究表明，围产期营养状况建立了一个营养敏感的记忆，增强肝脏自噬在晚年，这一过程可能作为一种保护机制，以有限的营养。
Intrauterine growth restriction (IUGR) leads to adult obesity, cardiovascular disease, and non-alcoholic fatty liver disease/steatohepatitis. Animal models have shown that combined intrauterine and early postnatal calorie restriction (IPCR) ameliorates these sequelae in adult life. The mechanism by which IPCR protects against adult onset disease is not understood. Autophagy, a lysosomal degradative process, recycles cellular constituents and eliminates damaged organelles, proteins, and oxidants. In this study, we hypothesized that IPCR could regulate autophagy in the liver of male rat offspring. At birth (d1) of male IUGR rat offspring and on day 21 (p21) of life, IPCR male rat offspring had a profound decrease in hepatic autophagy in all three stages of development: initiation, elongation, and maturation. However, upon receiving a normal diet ad-lib throughout adulthood, aged IPCR rats (day 450 of life (p450)), had increased hepatic autophagy, in direct contrast to what was seen in early life. The decreased autophagy at d21 led to the accumulation of ubiquitinated proteins and lipid oxidative products, whereas the increased autophagy in late life had the opposite effect. Oxidized lipids were unchanged at d1 by IUGR treatment indicating that decreased autophagy precedes oxidative stress in early life. When cellular signaling pathways regulating autophagy were examined, the 5′ adenosine monophosphate-activated protein kinase pathway (AMPK), and not endoplasmic stress pathways, was found to be altered, suggesting that autophagy is regulated through AMPK signaling pathway in IPCR rats. Taken together, this study reveals that the perinatal nutritional status establishes a nutritionally sensitive memory that enhances hepatic autophagy in late life, a process that perhaps acts as a protective mechanism to limited nutrition.
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影响因子：
--
作者：
Guillaumet-Adkins A;Yañez Y;Peris-Diaz MD;Calabria I;Palanca-Ballester C;Sandoval J
通讯作者：
Sandoval J
DOI：
10.1177/1535370213489446
发表时间：
2013-05
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
--
作者：
Manley S;Williams JA;Ding WX
通讯作者：
Ding WX
DOI：
10.1016/j.bbadis.2004.11.025
发表时间：
2005-06-30
影响因子：
6.2
作者：
Rajasekaran, NS;Sathyanarayanan, S;Devaraj, H
通讯作者：
Devaraj, H
影响因子：
4.8
作者：
Jain, Ashish;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
9
作者：
通讯作者：
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