Wang Wei, Fromm Michael
Department of Animal Science, University of Nebraska, Lincoln, Nebraska, United States of America.
Center for Biotechnology, University of Nebraska, Lincoln, Nebraska, United States of America.
PLoS One. 2015 Apr 23;10(4):e0119005. doi: 10.1371/journal.pone.0119005. eCollection 2015.
Conjugated linoleic acid (CLA) reduces adiposity in human and mouse adipocytes. This outcome is achieved through a variety of biological responses including increased energy expenditure and fatty acid oxidation, increased inflammation, repression of fatty acid biosynthesis, attenuated glucose transport, and apoptosis. In the current study, profiling of 261 metabolites was conducted to gain new insights into the biological pathways responding to CLA in 3T3-L1 adipocytes. Sphinganine and sphingosine levels were observed to be highly elevated in CLA treated adipocytes. Exogenous chemicals that increased endogenous ceramide levels decreased lipid levels in adipocytes, and activated AMP-activated protein kinase (AMPK) as well as NF-κB, both of which are typically activated in CLA treated adipocytes. Concurrent inhibition of ceramide de novo biosynthesis and recycling from existing sphingolipid pools attenuated the lipid lowering effect normally associated with responses to CLA, implicating ceramides as an important component of the lipid lowering response in CLA treated adipocytes.
共轭亚油酸(CLA)可降低人和小鼠脂肪细胞中的肥胖程度。这一结果是通过多种生物学反应实现的,包括增加能量消耗和脂肪酸氧化、增强炎症反应、抑制脂肪酸生物合成、减弱葡萄糖转运以及诱导细胞凋亡。在本研究中,对261种代谢物进行了分析,以深入了解3T3-L1脂肪细胞中对CLA产生反应的生物学途径。结果发现,CLA处理的脂肪细胞中鞘氨醇和鞘氨醇水平显著升高。增加内源性神经酰胺水平的外源化学物质可降低脂肪细胞中的脂质水平,并激活AMP激活的蛋白激酶(AMPK)以及NF-κB,这两种物质在CLA处理的脂肪细胞中通常也会被激活。同时抑制神经酰胺的从头生物合成以及从现有鞘脂池中回收,会减弱通常与CLA反应相关的脂质降低效应,这表明神经酰胺是CLA处理的脂肪细胞中脂质降低反应的重要组成部分。