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PPAR alpha and PPAR gamma activation attenuates total free fatty acid and triglyceride accumulation in macrophages via the inhibition of Fatp1 expression

文献类型：期刊论文

作者Ye, Guozhu2,4; Gao, Han1,2; Wang, Zhichao1,3; Lin, Yi2; Liao, Xu2; Zhang, Han2; Chi, Yulang2; Zhu, Huimin2; Dong, Sijun2,4
刊名CELL DEATH & DISEASE
出版日期2019-01-15
卷号10页码:14
ISSN号2041-4889
DOI10.1038/s41419-018-1135-3
通讯作者Dong, Sijun(sjdong@iue.ac.cn)
英文摘要Lipid accumulation in macrophages interacts with microenvironment signals and accelerates diabetic atherosclerosis. However, the molecular mechanisms by which macrophage metabolism interacts with microenvironment signals during lipid accumulation are not clearly understood. Accordingly, an untargeted metabolomics approach was employed to characterize the metabolic reprogramming, and to identify potential regulatory targets related to lipid accumulation in macrophages treated with oleate, an important nutrient. The metabolomics approach revealed that multiple metabolic pathways were significantly disturbed in oleate-treated macrophages. We discovered that amino acids, nucleosides, lactate, monoacylglycerols, total free fatty acids (FFAs), and triglycerides (TGs) accumulated in oleate-treated macrophages, but these effects were effectively attenuated or even abolished by resveratrol. Notably, 1-monooleoylglycerol and 2-monooleoylglycerol showed the largest fold changes in the levels among the differential metabolites. Subsequently, we found that oleate triggered total FFA and TG accumulation in macrophages by accelerating FFA influx through the activation of Fatp1 expression, but this effect was attenuated by resveratrol via the activation of PPAR alpha and PPAR gamma signaling. We verified that the activation of PPAR alpha and PPAR gamma by WY14643 and pioglitazone, respectively, attenuated oleate triggered total FFA and TG accumulation in macrophages by repressing FFA import via the suppression of Fatp1 expression. Furthermore, the inhibition of Fatp1 by tumor necrosis factor a alleviated oleate-induced total FFA and TG accumulation in macrophages. This study provided the first demonstration that accumulation of amino acids, nucleosides, lactate, monoacylglycerols, total FFAs, and TGs in oleate-treated macrophages is effectively attenuated or even abolished by resveratrol, and that the activation of PPAR alpha and PPAR gamma attenuates oleate-induced total FFA and TG accumulation via suppression of Fatp1 expression in macrophages. Therapeutic strategies aim to activate PPAR signaling, and to repress FFA import and triglyceride synthesis are promising approaches to reduce the risk of obesity, diabetes and atherosclerosis.
WOS关键词INSULIN-RESISTANCE ; OXIDATIVE STRESS ; IMMUNOMETABOLISM ; CELL ; METABOLISM
资助项目National Natural Science Foundation of China[21507128] ; National Natural Science Foundation of China[41390240] ; National Natural Science Foundation of China[21777158] ; National Natural Science Foundation of China[21477124] ; National Natural Science Foundation of China[21677140] ; Natural Science Foundation of Fujian Province, China[2018J01020] ; Science and Technology Program of Fujian Province[2016T3005] ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences[J008]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000472750600007
出版者NATURE PUBLISHING GROUP
资助机构National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Fujian Province, China ; Natural Science Foundation of Fujian Province, China ; Science and Technology Program of Fujian Province ; Science and Technology Program of Fujian Province ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Fujian Province, China ; Natural Science Foundation of Fujian Province, China ; Science and Technology Program of Fujian Province ; Science and Technology Program of Fujian Province ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Fujian Province, China ; Natural Science Foundation of Fujian Province, China ; Science and Technology Program of Fujian Province ; Science and Technology Program of Fujian Province ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Natural Science Foundation of Fujian Province, China ; Natural Science Foundation of Fujian Province, China ; Science and Technology Program of Fujian Province ; Science and Technology Program of Fujian Province ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences ; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences
源URL[http://cas-ir.dicp.ac.cn/handle/321008/175913]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Dong, Sijun
作者单位1.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China
2.Chinese Acad Sci, Inst Urban Environm, Key Lab Urban Environm & Hlth, 1799 Jimei Rd, Xiamen 361021, Fujian, Peoples R China
3.Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, 457 Zhongshan Rd, Dalian 116023, Peoples R China
4.Chinese Acad Sci, Ctr Excellence Reg Atmospher Environm, Inst Urban Environm, 1799 Jimei Rd, Xiamen 361021, Fujian, Peoples R China
推荐引用方式
GB/T 7714		 Ye, Guozhu,Gao, Han,Wang, Zhichao,et al. PPAR alpha and PPAR gamma activation attenuates total free fatty acid and triglyceride accumulation in macrophages via the inhibition of Fatp1 expression[J]. CELL DEATH & DISEASE,2019,10:14.
APA Ye, Guozhu.,Gao, Han.,Wang, Zhichao.,Lin, Yi.,Liao, Xu.,...&Dong, Sijun.(2019).PPAR alpha and PPAR gamma activation attenuates total free fatty acid and triglyceride accumulation in macrophages via the inhibition of Fatp1 expression.CELL DEATH & DISEASE,10,14.
MLA Ye, Guozhu,et al."PPAR alpha and PPAR gamma activation attenuates total free fatty acid and triglyceride accumulation in macrophages via the inhibition of Fatp1 expression".CELL DEATH & DISEASE 10(2019):14.

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