DOI: 10.1016/j.scib.2020.07.023
论文题名: 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
作者: Lam S.M. ; Zhou T. ; Li J. ; Zhang S. ; Chua G.H. ; Li B. ; Shui G.
刊名: Science Bulletin
ISSN: 20959273
出版年: 2020
卷: 65, 期: 21 起始页码: 1840
结束页码: 1848
语种: 英语
中文关键词: 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
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 Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/169942
Appears in Collections: 气候变化与战略
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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
Recommended Citation:
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]. Science Bulletin,2020-01-01,65(21)