Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine model.
Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine model.
复制标题
DOI：
10.1016/j.metabol.2009.11.006
复制
发表时间：
2010-08
影响因子：
9.8
通讯作者：
Puder, Mark
中科院分区：
文献类型：
--
作者：
de Meijer, Vincent E.;Le, Hau D.;Meisel, Jonathan A.;Sharif, M. Reza Akhavan;Pan, Amy;Nose, Vania;Puder, Mark
非酒精性脂肪性肝病（NAFLD）是由过度消费引起的，是肝衰竭的一个重要且日益增加的原因。有利于这种疾病发展的饮食类型尚未确定，目前缺乏循证治疗方案。我们假设肝脂肪变性的发生与高脂肪含量的饮食有关，而不是与过量的热量摄入有关。此外，我们还假设，完全表现的肝脂肪变性可以通过降低肥胖小鼠饮食中的脂肪百分比来逆转。C57 Bl/6 J雄性小鼠喂食含有10%脂肪的纯化啮齿动物饮食或含有60%来自脂肪的卡路里的饮食。采用配对喂养设计，以区分膳食脂肪含量和热量摄入对膳食诱导的肝脏脂质蓄积和相关损伤的影响。通过定量RT-PCR分析肝脏的脂质代谢相关基因表达。9周后，与摄入相同热量的10%脂肪饮食的小鼠相比，摄入60%脂肪饮食的小鼠表现出更多的体重增加、胰岛素抵抗和肝脏脂肪变性。此外，在9周时已建立代谢综合征的小鼠在转换为10%脂肪饮食额外9周时显示出肝脏脂肪变性、胰岛素抵抗和肥胖的逆转，与热量摄入无关。定量RT-PCR显示，与新生脂肪生成和游离脂肪酸摄取增加相关的转录物在成对喂食60%脂肪饮食的小鼠中显着上调，与喂食10%脂肪的动物相比。在C57 Bl/6 J饮食诱导的肥胖模型中，膳食脂肪含量（独立于热量摄入）是肝脂肪变性、肥胖和胰岛素抵抗发展的关键因素，该模型由游离脂肪酸摄取增加和从头脂肪生成引起。此外，一旦建立，所有这些代谢综合征的特征都可以在将肥胖小鼠转换为低脂肪饮食后成功逆转。低脂饮食在NAFLD患者的潜在治疗研究中值得关注。
Non-alcoholic fatty liver disease (NAFLD) results from over-consumption and is a significant and increasing cause of liver failure. The type of diet that is conducive to the development of this disease has not been established and evidence-based treatment options are currently lacking. We hypothesized that the onset of hepatic steatosis is linked to the consumption of a diet with a high fat content, rather than related to excess caloric intake. In addition, we also hypothesized that fully manifested hepatic steatosis could be reversed by reducing the fat percentage in the diet of obese mice. C57Bl/6J male mice were either fed a purified rodent diet containing 10% fat or a diet with 60% of calories derived from fat. A pair-feeding design was used to distinguish the effects of dietary fat content and caloric intake on dietary-induced hepatic lipid accumulation and associated injury. Livers were analyzed by quantitative RT-PCR for lipid metabolism-related gene expression. After 9 weeks, mice on the 60% fat diet exhibited more weight gain, insulin resistance and hepatic steatosis, compared to mice on a 10% fat diet with equal caloric intake. Furthermore, mice with established metabolic syndrome at 9 weeks showed reversal of hepatic steatosis, insulin resistance and obesity when switched to a 10% fat diet for an additional 9 weeks, independent of caloric intake. Quantitative RT-PCR revealed that transcripts related to both de novo lipogenesis and increased uptake of free fatty acids were significantly upregulated in mice pair-fed a 60% fat diet, compared to 10% fat-fed animals. Dietary fat content, independent from caloric intake, is a crucial factor in the development of hepatic steatosis, obesity and insulin resistance in the C57Bl/6J diet-induced obesity model caused by increased uptake of free fatty acids and de novo lipogenesis. In addition, once established, all these features of the metabolic syndrome can be successfully reversed after switching obese mice to a diet low in fat. Low fat diets deserve attention in the investigation of a potential treatment of patients with NAFLD.
登录
查看更多内容
影响因子：
3.4
作者：
Astrup, Arne
通讯作者：
Astrup, Arne
影响因子：
4.8
作者：
Li, Zheng Zheng;Berk, Michael;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.
影响因子：
4.8
作者：
Fan, CY;Pan, J;Reddy, JK
通讯作者：
Reddy, JK
影响因子：
25.7
作者：
Popov, Y;Patsenker, E;Schuppan, D
通讯作者：
Schuppan, D
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH