Maternal resveratrol intake during lactation attenuates hepatic triglyceride and fatty acid synthesis in adult male rat offspring.
Maternal resveratrol intake during lactation attenuates hepatic triglyceride and fatty acid synthesis in adult male rat offspring.
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DOI：
10.1016/j.bbrep.2016.12.011
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发表时间：
2017-03
影响因子：
2.7
通讯作者：
Saito T
中科院分区：
文献类型：
--
作者：
Tanaka M;Kita T;Yamasaki S;Kawahara T;Ueno Y;Yamada M;Mukai Y;Sato S;Kurasaki M;Saito T
白藜芦醇（3,5,4-三羟基二苯乙烯）是葡萄和红酒中发现的一种天然多酚化合物，已被证明对肝脏具有保护作用，可以防止高脂肪饮食引起的脂质积累。然而，没有研究表明，营养白藜芦醇的摄入量由亲代改变脂肪生成的成年后代。本研究旨在探讨哺乳期母鼠摄入白藜芦醇是否会影响成年雄性大鼠后代的脂肪生成，如果有影响，其分子机制是什么。6只母鼠在哺乳期饲喂对照饲粮（CC组），6只母鼠在哺乳期饲喂对照饲粮和白藜芦醇（CR组），饲喂标准饲粮直至36周牺牲。哺乳期给予白藜芦醇（CR组）的成年雄性后代从哺乳期第四周到成年体重较低，但相对食物摄入量没有明显变化。与CC组相比，CR组的血浆甘油三酯水平较低。对成年雄性大鼠后代肝脏的组织病理学分析显示，CC组肝细胞中脂质积累，而CR组很少出现脂滴。与CC组相比，CR组中ser403、Sirt1和Nampt位点磷酸化的ampk肝脏蛋白水平显著上调。这些结果表明，哺乳期母体摄入白藜芦醇通过上调Sirt1诱导AMPK激活。在本研究中，与CC组相比，CR组显著上调了甾醇调节元件结合蛋白1c （SREBP-1c）前体水平，下调了活性SREBP-1c/前体SREBP-1c的比例。这些结果表明，在CR组肝脏中，AMPK抑制了SREBP-1c的蛋白水解过程。众所周知，SREBP-1c通过激活参与甘油三酯和脂肪酸合成的基因来调节脂肪生成途径。本研究显示，CR组肝脏脂肪酸合成酶（FAS）和乙酰辅酶a羧化酶（ACC）水平显著下调。这些结果表明，哺乳期母体摄入白藜芦醇可抑制成年雄性后代肝脏中SREBP-1c的裂解和核易位，并抑制SREBP-1c靶基因FAS和ACC的表达。这些变化减弱了成年雄性后代肝脏中三酰甘油和脂肪酸的合成。哺乳期母鼠摄入白藜芦醇可降低成年雄性大鼠后代肝脏甘油三酯和脂肪酸的合成。母鼠在哺乳期摄入白藜芦醇可通过上调成年雄性大鼠后代肝脏中的Sirt1诱导AMPK的激活。哺乳期间母体摄入白藜芦醇可抑制成年雄性大鼠后代肝脏中SREBP-1c和SREBP-1c靶基因（如FAS和ACC）的蛋白水解过程。
Resveratrol (3,5,4-trihydroxystilbene) is a natural polyphenolic compound found in grapes and red wine and has been shown to exert protective effects on the liver preventing lipid accumulation induced by a high-fat diet. However, no studies have shown that the nutritional resveratrol intake by the parental generation has modified lipogenesis in an adult offspring. The aim of this study was to investigate whether maternal resveratrol intake during lactation affects lipogenesis in adult male rat offspring, and if it does, what is the molecular mechanistic basis. Six male pups born from mothers given a control diets during lactation (CC group) and six male pups born from mothers given a control diet as well as resveratrol during lactation (CR group) were fed a standard diet until sacrifice at 36 weeks. Adult male offspring from mothers given resveratrol during lactation (CR group) had lower body weight from the fourth week of lactation until adulthood, but no significant change was observed in the relative food intake. Low levels of plasma triacylglycerol were found in the CR group compared to the CC group. Histopathological analysis of the livers of adult male rat offspring revealed lipid accumulation in hepatocytes in the CC group, whereas lipid droplets were rare in the CR group. Hepatic protein levels of AMPK-phosphorylated at ser403, Sirt1, and Nampt in the CR group were upregulated significantly compared to the CC group. These results indicated the maternal resveratrol intake during lactation-induced activation of AMPK through Sirt1 upregulation. In this study, significant upregulation of the levels of precursor of sterol regulatory element binding protein-1c (SREBP-1c) and downregulation of the ratio of active-SREBP-1c/precusor-SREBP-1c were observed in the CR group compared to the CC group. These results suggested that proteolytic processing of SREBP-1c was suppressed by AMPK in the livers of the CR group. It is well known that SREBP-1c regulates the lipogenic pathway by activating genes involved in triglyceride and fatty acid synthesis. The present study showed significant downregulation of hepatic fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) levels in the CR group. These results indicated that maternal resveratrol intake during lactation suppressed SREBP-1c cleavage and nuclear translocation and repressed SREBP-1c target gene expression such as FAS and ACC in the livers of adult male offspring. These changes attenuate hepatic triacylglycerol and fatty acid synthesis in adult male offspring. Maternal resveratrol intake during lactation attenuates hepatic triglyceride and fatty acid synthesis in adult male rat offspring. Maternal resveratrol intake during lactation induces the activation of AMPK through Sirt1 upregulation in the livers of adult male rat offspring. Maternal resveratrol intake during lactation suppressed the proteolytic processing of SREBP-1c and SREBP-1c target gene expression, such as FAS and ACC, in the livers of adult male rat offspring.