Linoleic acid and stearic acid elicit opposite effects on AgRP expression and secretion via TLR4-dependent signaling pathways in immortalized hypothalamic N38 cells.
Linoleic acid and stearic acid elicit opposite effects on AgRP expression and secretion via TLR4-dependent signaling pathways in immortalized hypothalamic N38 cells.
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亚油酸和硬脂酸通过 TLR4 依赖性信号通路在永生化下丘脑 N38 细胞中对 AgRP 表达和分泌产生相反的影响。
DOI：
10.1016/j.bbrc.2016.02.031
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Jiang Qingyan
中科院分区：
文献类型：
--
作者：
Wang Songbo;Xiang Nana;Yang Liusong;Zhu Canjun;Zhu Xiaotong;Wang Lina;Gao Ping;Xi Qianyun;Zhang Yongliang;Shu Gang;Jiang Qingyan
控制食物摄入是对抗肥胖的一种很有希望的方法。研究表明，不同的脂肪酸对食物摄入和体重有不同的影响。然而，其潜在的机制仍然知之甚少。本研究旨在探讨亚油酸（LA）和硬脂酸（SA）对永生化小鼠下丘脑N38细胞中AgRP相关蛋白（AgRP）表达和分泌的影响，并探讨其可能的机制。我们的研究结果表明，LA抑制，而SA刺激AgRP的表达和N38细胞的分泌呈剂量依赖性。此外，LA抑制toll样受体4 （TLR4）蛋白表达、JNK和IKKalpha/beta磷酸化水平，提示TLR4依赖性炎症通路受到抑制。然而，LA的上述抑制作用被TLR4激动剂脂多糖（LPS）消除。相反，SA促进TLR4蛋白表达，激活TLR4依赖性炎症通路，p-JNK/JNK比值升高。而TLR4 siRNA逆转了SA对AgRP表达和TLR4依赖性炎症的刺激作用。此外，我们发现TLR4还参与了N38细胞中la增强和sa受损的瘦素/胰岛素信号通路。综上所述，我们的研究结果表明，LA通过tlr4依赖性炎症和瘦素/胰岛素途径对N38细胞中AgRP的表达和分泌产生抑制作用，而SA通过tlr4依赖性炎症和瘦素/胰岛素途径对AgRP产生刺激作用。这些数据提供了对脂肪酸调节食物摄入的机制的更好理解，并提示了长链不饱和脂肪酸如LA在减少食物摄入和治疗肥胖方面的潜在作用。
The regulation of food intake is a promising way to combat obesity. It has been implicated that various fatty acids exert different effects on food intake and body weight. However, the underlying mechanism remains poorly understood. The aim of the present study was to investigate the effects of linoleic acid (LA) and stearic acid (SA) on agouti-related protein (AgRP) expression and secretion in immortalized mouse hypothalamic N38 cells and to explore the likely underlying mechanisms. Our results demonstrated that LA inhibited, while SA stimulated AgRP expression and secretion of N38 cells in a dose-dependent manner. In addition, LA suppressed the protein expression of toll-like receptor 4 (TLR4), phosphorylation levels of JNK and IKKalpha/beta, suggesting the inhibition of TLR4-dependent inflammation pathway. However, the above mentioned inhibitory effects of LA were eliminated by TLR4 agonist lipopolysaccharide (LPS). In contrast, SA promoted TLR4 protein expression and activated TLR4-dependent inflammation pathway, with elevated ratio of p-JNK/JNK. While TLR4 siRNA reversed the stimulatory effects of SA on AgRP expression and TLR4-dependent inflammation. Moreover, we found that TLR4 was also involved in LA-enhanced and SA-impaired leptin/insulin signal pathways in N38 cells. In conclusion, our findings indicated that LA elicited inhibitory while SA exerted stimulatory effects on AgRP expression and secretion via TLR4-dependent inflammation and leptin/insulin pathways in N38 cells. These data provided a better understanding of the mechanism underlying fatty acids-regulated food intake and suggested the potential role of long-chain unsaturated fatty acids such as LA in reducing food intake and treating obesity.
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DOI：
10.1096/fasebj.29.1_supplement.746.2
发表时间：
2015-04
期刊：
The FASEB Journal
影响因子：
--
作者：
Kyle J. Mamounis;T. Roepke
通讯作者：
Kyle J. Mamounis;T. Roepke
影响因子：
1.4
作者：
Toledo, Karen;Aranda, Mario;Bustos, Paulina
通讯作者：
Bustos, Paulina
影响因子：
4.8
作者：
Rother, Eva;Kuschewski, Ruth;Doetsch, Joerg
通讯作者：
Doetsch, Joerg
影响因子：
3.3
作者：
Everson-Rose SA;Ryan JP
通讯作者：
Ryan JP
DOI：
10.1016/j.plefa.2006.05.012
发表时间：
2006-09-01
影响因子：
3
作者：
Calder, Philip C.
通讯作者：
Calder, Philip C.