Intercollegiate Faculty of Nutrition, Department of Nutrition and Food Science, Texas A&M University, College Station, Texas, United States of America.
PLoS One. 2012;7(6):e39286. doi: 10.1371/journal.pone.0039286. Epub 2012 Jun 29.
The interaction between fat deposition and inflammation during obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD). The present study examined the effects of palmitoleate, a monounsaturated fatty acid (16:1n7), on liver metabolic and inflammatory responses, and investigated the mechanisms by which palmitoleate increases hepatocyte fatty acid synthase (FAS) expression. Male wild-type C57BL/6J mice were supplemented with palmitoleate and subjected to the assays to analyze hepatic steatosis and liver inflammatory response. Additionally, mouse primary hepatocytes were treated with palmitoleate and used to analyze fat deposition, the inflammatory response, and sterol regulatory element-binding protein 1c (SREBP1c) activation. Compared with controls, palmitoleate supplementation increased the circulating levels of palmitoleate and improved systemic insulin sensitivity. Locally, hepatic fat deposition and SREBP1c and FAS expression were significantly increased in palmitoleate-supplemented mice. These pro-lipogenic events were accompanied by improvement of liver insulin signaling. In addition, palmitoleate supplementation reduced the numbers of macrophages/Kupffer cells in livers of the treated mice. Consistently, supplementation of palmitoleate decreased the phosphorylation of nuclear factor kappa B (NF-κB, p65) and the expression of proinflammatory cytokines. These results were recapitulated in primary mouse hepatocytes. In terms of regulating FAS expression, treatment of palmitoleate increased the transcription activity of SREBP1c and enhanced the binding of SREBP1c to FAS promoter. Palmitoleate also decreased the phosphorylation of NF-κB p65 and the expression of proinflammatory cytokines in cultured macrophages. Together, these results suggest that palmitoleate acts through dissociating liver inflammatory response from hepatic steatosis to play a unique role in NAFLD.
在肥胖过程中，脂肪沉积与炎症的相互作用导致非酒精性脂肪性肝病（NAFLD）的发生。本研究探讨了棕榈油酸（16:1n7，一种单不饱和脂肪酸）对肝脏代谢和炎症反应的影响，并研究了棕榈油酸增加肝细胞脂肪酸合酶（FAS）表达的机制。雄性野生型 C57BL/6J 小鼠补充棕榈油酸并进行检测，以分析肝脂肪变性和肝脏炎症反应。此外，还使用小鼠原代肝细胞进行检测，以分析脂肪沉积、炎症反应和固醇调节元件结合蛋白 1c（SREBP1c）的激活。与对照组相比，棕榈油酸补充增加了循环棕榈油酸水平并改善了全身胰岛素敏感性。局部来看，棕榈油酸补充显著增加了肝脂肪沉积和 SREBP1c 和 FAS 的表达。这些促脂肪生成事件伴随着肝脏胰岛素信号的改善。此外，棕榈油酸补充减少了治疗小鼠肝脏中巨噬细胞/库普弗细胞的数量。一致地，棕榈油酸补充降低了核因子 kappa B（NF-κB，p65）的磷酸化和促炎细胞因子的表达。这些结果在原代小鼠肝细胞中得到了重现。在调节 FAS 表达方面，棕榈油酸处理增加了 SREBP1c 的转录活性，并增强了 SREBP1c 与 FAS 启动子的结合。棕榈油酸还降低了培养的巨噬细胞中 NF-κB p65 的磷酸化和促炎细胞因子的表达。综上所述，棕榈油酸通过将肝脏炎症反应与肝脂肪变性分离来发挥其在非酒精性脂肪性肝病中的独特作用。
