Background

Fatty acids (FAs), and especially monounsaturated FAs (MUFAs) stimulate GLP-1 release. However, lipotoxicity is indicated in GLP-1 secreting cells following long-term exposure to elevated levels of saturated FAs (SFAs) in vivo and in vitro, where in vitro studies indicate that cosupplementation with MUFAs confers lipoprotection. SFAs and MUFAs differentially affect the fate of cells in ways that depend on the cell type, concentration and ratio of the FAs. The present study was designed to further elucidate the mechanisms underlying the effects of SFAs/MUFAs on GLP-1-producing cells in terms of lipotoxicity/lipoprotection and GLP-1 secretion.

Methods

Cultured GLP-1 secreting cells were exposed to hyperlipidemia simulated by SFA-albumin complexes where the molar ratio was 2:1. The cellular response to simulated hyperlipidemia was assessed in the presence/absence of MUFA cosupplementation by determining intracellular ceramide, ROS, neutral lipid accumulation, and cellular respiration. The role for cellular respiration in GLP-1 secretion in response to SFAs/MUFAs was assessed.

Results

Generation of intracellular ceramide mediate a detrimental increased in ROS production following long term exposure to SFAs in GLP-1-secreting cells. Cosupplementation with MUFAs increases cellular respiration, triglyceride synthesis, and the expression of ceramide kinase, while reducing ceramide synthesis and attenuating ROS production, caspase-3 activity and DNA fragmentation. Further, acute secretory effects of unsaturated FAs are independent of FAO, but mediated by a FFAR1 induced increase in cellular respiration.

Conclusion

This study demonstrates novel data supporting effects of MUFAs on the ceramide biosynthetic pathway, triglyceride storage respiration and secretion in GLP-1 secreting cells. These findings may be of value for nutritional interventions, as well as for identification of novel targets, to help preserve L-cell mass and potentiate GLP-1 secretion in diabesity.

中文翻译：

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油酸通过减少神经酰胺诱导的ROS来增加中性脂质积累，细胞呼吸并拯救棕榈酸酯暴露的GLP-1分泌细胞

背景

脂肪酸（FAs），尤其是单不饱和FAs（MUFAs）刺激GLP-1的释放。但是，在体内和体外长期暴露于升高水平的饱和FAs（SFA）后，分泌GLP-1的细胞表现出脂毒性，其中体外研究表明，与MUFA共同补充赋予了脂保护作用。SFA和MUFA取决于细胞的类型，浓度和比例，以不同方式影响细胞的命运。本研究旨在从脂毒性/脂保护和GLP-1分泌方面进一步阐明SFA / MUFA对GLP-1产生细胞的影响的潜在机制。

方法

通过SFA-白蛋白复合物模拟摩尔比为2：1的培养的分泌GLP-1的细胞暴露于高脂血症。通过确定细胞内神经酰胺，ROS，中性脂质蓄积和细胞呼吸，在存在/不存在MUFA辅食的情况下评估对模拟高脂血症的细胞反应。评估了细胞呼吸在响应SFA / MUFA的GLP-1分泌中的作用。

结果

长期暴露于分泌GLP-1的细胞中的SFA后，细胞内神经酰胺的产生介导了ROS产生的有害增加。与MUFA共同补充可增加细胞呼吸作用，甘油三酸酯合成和神经酰胺激酶的表达，同时减少神经酰胺合成并减弱ROS的产生，caspase-3活性和DNA片段化。此外，不饱和脂肪酸的急性分泌作用与粮农组织无关，但由FFAR1诱导的细胞呼吸增加介导。

结论

这项研究证明了支持MUFA对神经酰胺生物合成途径，甘油三酯储存呼吸和GLP-1分泌细胞分泌的影响的新数据。这些发现可能对营养干预以及新靶标的识别具有重要意义，有助于维持L细胞的质量并增强糖尿病中GLP-1的分泌。