Peroxisome Proliferator-Activated Receptor α Has a Protective Effect on Fatty Liver Caused by Excessive Sucrose Intake.
Peroxisome Proliferator-Activated Receptor α Has a Protective Effect on Fatty Liver Caused by Excessive Sucrose Intake.
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DOI：
10.3390/biomedicines10092199
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发表时间：
2022-09-06
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
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甾醇调节元件结合蛋白 (SREBP)-1c 是一种转录因子，可调节肝脏中葡萄糖的脂质合成。它被蔗糖激活，从而激活脂肪酸合成途径。另一方面，过氧化物酶体增殖物激活受体 (PPAR) α 调节编码参与肝脏脂肪酸 β-氧化的酶的多个基因的转录。为了评估 PPARα 对过量蔗糖摄入引起的脂肪肝的有益作用，我们研究了喂食高蔗糖饮食 (Suc) 的 PPARα 缺陷小鼠中与脂肪肝发生相关的分子机制。摄入蔗糖会增加 SREBP-1c 靶基因的表达，从而导致脂肪肝的发生。此外，PPARα−/− 小鼠出现了严重的脂肪肝。饲喂 Suc 的雄性和雌性 PPARα−/− 小鼠的肝脏脂肪含量分别比饲喂 Suc 的雄性和雌性野生型小鼠高 3.7 倍和 3.1 倍。因此，PPARα可能有助于预防因蔗糖摄入过多而引起的脂肪肝的发生。雄性和雌性 PPARα−/− 小鼠的肝脏 TG 积累不同。一种可能的解释是，雄性小鼠表现出 Pparγ 表达增加，这通常有助于肝脏中甘油三酯的合成，以补偿 Pparα 的缺乏。相比之下，雌性野生型小鼠天生具有较低的 Pparα 水平。因此，Pparα 缺乏对雌性小鼠的影响不太明显。激活 PPARα 的饮食可能能有效预防因蔗糖摄入过多而导致的脂肪肝。
Sterol regulatory element binding protein (SREBP)-1c is a transcription factor that regulates lipid synthesis from glucose in the liver. It is activated by sucrose, which activates the fatty acid synthesis pathway. On the other hand, peroxisome proliferator-activated receptor (PPAR) α regulates the transcription of several genes encoding enzymes involved in fatty acid β-oxidation in the liver. To evaluate the beneficial effects of PPARα on fatty liver caused by excessive sucrose intake, we investigated the molecular mechanisms related to the development of fatty liver in PPARα-deficient mice that were fed a high-sucrose diet (Suc). The SREBP-1c target gene expression was increased by sucrose intake, leading to the development of fatty liver. Furthermore, PPARα−/− mice developed severe fatty liver. Male and female PPARα−/− mice fed Suc showed 3.7- and 3.1-fold higher liver fat content than Suc-fed male and female wild-type mice, respectively. Thus, PPARα may work to prevent the development of fatty liver caused by excessive sucrose intake. Liver TG accumulation differed between male and female PPARα−/− mice. A possible explanation is that male mice show the increased expression of Pparγ, which usually contributes to triglyceride synthesis in the liver, to compensate for Pparα deficiency. In contrast, female wild-type mice inherently have low Pparα levels. Thus, Pparα deficiency has less pronounced effects in female mice. A diet that activates PPARα may be effective for preventing the development of fatty liver due to excessive sucrose intake.
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影响因子：
4.8
作者：
Jalouli, M;Carlsson, L;Oscarsson, J
通讯作者：
Oscarsson, J
胰岛素对大鼠肝脏，人和大鼠脂肪组织中胰岛素对SREBP-1C激活和Insig-1/2的体内影响的比较。
影响因子：
6.9
作者：
Boden, Guenther;Salehi, Sajad;Cheung, Peter;Homko, Carol;Song, Weiwei;Loveland-Jones, Catherine;Jayarajan, Senthil
通讯作者：
Jayarajan, Senthil
DOI：
10.1073/pnas.96.20.11041
发表时间：
1999-09-28
影响因子：
11.1
作者：
Brown, MS;Goldstein, JL
通讯作者：
Goldstein, JL
DOI：
10.1152/ajpendo.90248.2008
发表时间：
2008-10-01
影响因子：
5.1
作者：
Bryzgalova, Galyna;Lundholm, Lovisa;Dahlman-Wright, Karin
通讯作者：
Dahlman-Wright, Karin
影响因子：
29.4
作者：
Eslam, Mohammed;Sanyal, Arun J.;George, Jacob
通讯作者：
George, Jacob