气候变化领域集成服务门户(CCPortal): A robust, integrated platform for comprehensive analyses of acyl-coenzyme As and acyl-carnitines revealed chain length-dependent disparity in fatty acyl metabolic fates across Drosophila development

CCPortal

DOI	10.1016/j.scib.2020.07.023
	A robust, integrated platform for comprehensive analyses of acyl-coenzyme As and acyl-carnitines revealed chain length-dependent disparity in fatty acyl metabolic fates across Drosophila development
	Lam S.M.; Zhou T.; Li J.; Zhang S.; Chua G.H.; Li B.; Shui G.
发表日期	2020
ISSN	20959273
起始页码	1840
结束页码	1848
卷号	65 期号:21
英文摘要	Acyl-coenzyme A thioesters (acyl-CoAs) denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways. The great diversity in polarity between short- and long-chain acyl-CoAs makes it technically challenging to cover an inclusive range of acyl-CoAs within a single method. Levels of acyl-carnitines, which function to convey fatty acyls into mitochondria matrix for β-oxidation, indicate the efficiency of mitochondrial import and utilization of corresponding acyl-CoAs. Herein, we report a robust, integrated platform to allow simultaneous quantitation of endogenous acyl-CoAs and acyl-carnitines. Using this method, we monitored changes in intermediary lipid profiles across Drosophila development under control (ND) and high-fat diet (HFD). We observed specific accumulations of medium-chain (C8–C12) and long-chain (≥C16) acyl-carnitines distinct to L3 larval and pupal stages, respectively. These observations suggested development-specific, chain length-dependent disparity in metabolic fates of acyl-CoAs across Drosophila development, which was validated by deploying the same platform to monitor isotope incorporation introduced from labelled 12:0 and 16:0 fatty acids into extra- and intra-mitochondrial acyl-CoA pools. We found that pupal mitochondria preferentially import and oxidise C12:0-CoAs (accumulated as C12:0-carnitines in L3 stage) over C16:0-CoAs. Preferential oxidation of medium-chain acyl-CoAs limits mitochondrial utilization of long-chain acyl-CoAs (C16–C18), leading to pupal-specific accumulation of long-chain acyl-carnitines mediated by enhanced CPT1-6A activity. HFD skewed C16:0-CoAs towards catabolism over anabolism in pupa, thereby adversely affecting overall development. Our developed platform emphasizes the importance of integrating biological knowledge in the design of pathway-oriented platforms to derive maximal physiological insights from analysis of complex biological systems. © 2020 Science China Press
关键词	Acyl-carnitines Acyl-coenzyme As Drosophila Fatty acids High-fat diet β-Oxidation
英文关键词	Chain length; Coenzymes; Fatty acids; Metabolites; Mitochondria; Oxidation; Acyl-coenzymes; Beta oxidation; Complex biological systems; Comprehensive analysis; Integrated platform; Metabolic pathways; Mitochondrial import; Preferential oxidation; Metabolism
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207086
作者单位	State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; LipidALL Technologies Company Limited, Changzhou, 213022, China; University of Chinese Academy of Sciences, Beijing, 100049, China
推荐引用方式 GB/T 7714	Lam S.M.,Zhou T.,Li J.,et al. A robust, integrated platform for comprehensive analyses of acyl-coenzyme As and acyl-carnitines revealed chain length-dependent disparity in fatty acyl metabolic fates across Drosophila development[J],2020,65(21).
APA	Lam S.M..,Zhou T..,Li J..,Zhang S..,Chua G.H..,...&Shui G..(2020).A robust, integrated platform for comprehensive analyses of acyl-coenzyme As and acyl-carnitines revealed chain length-dependent disparity in fatty acyl metabolic fates across Drosophila development.Science Bulletin,65(21).
MLA	Lam S.M.,et al."A robust, integrated platform for comprehensive analyses of acyl-coenzyme As and acyl-carnitines revealed chain length-dependent disparity in fatty acyl metabolic fates across Drosophila development".Science Bulletin 65.21(2020).