title: High-Resolution Metabolomics with Acyl-CoA Profiling Reveals Widespread Remodeling in Response to Diet.
abstract: The availability of acyl-Coenzyme A (acyl-CoA) thioester compounds affects numerous cellular functions including autophagy, lipid oxidation and synthesis, and post-translational modifications. Consequently, the acyl-CoA level changes tend to be associated with other metabolic alterations that regulate these critical cellular functions. Despite their biological importance, this class of metabolites remains difficult to detect and quantify using current analytical methods. Here we show a universal method for metabolomics that allows for the detection of an expansive set of acyl-CoA compounds and hundreds of other cellular metabolites. We apply this method to profile the dynamics of acyl-CoA compounds and corresponding alterations in metabolism across the metabolic network in response to high fat feeding in mice. We identified targeted metabolites (>50) and untargeted features (>1000) with significant changes (FDR < 0.05) in response to diet. A substantial extent of this metabolic remodeling exhibited correlated changes in acyl-CoA metabolism with acyl-carnitine metabolism and other features of the metabolic network that together can lead to the discovery of biomarkers of acyl-CoA metabolism. These findings show a robust acyl-CoA profiling method and identify coordinated changes of acyl-CoA metabolism in response to nutritional stress.
authors: From the ‡Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853;
authors: Xiaojing
authors: X
authors: Liu
authors: §Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853;
authors: Sushabhan
authors: S
authors: Sadhukhan
authors: ¶Field of Biochemistry and Molecular Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853;
authors: Shengyi
authors: S
authors: Sun
authors: ‖Duke Molecular Physiology Institute, Duke University, Medical Center, Durham, North Carolina 27710; **Department of Medicine and Department of Pharmacology and Cancer Biology, Duke University, Medical Center, Durham, North Carolina 27710.
authors: Gregory R
authors: GR
authors: Wagner
authors: ‖Duke Molecular Physiology Institute, Duke University, Medical Center, Durham, North Carolina 27710; **Department of Medicine and Department of Pharmacology and Cancer Biology, Duke University, Medical Center, Durham, North Carolina 27710.
authors: Matthew D
authors: MD
authors: Hirschey
authors: From the ‡Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853; ¶Field of Biochemistry and Molecular Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853;
authors: Ling
authors: L
authors: Qi
authors: §Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853;
authors: Hening
authors: H
authors: Lin
authors: From the ‡Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853; ¶Field of Biochemistry and Molecular Cell Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853; Locasale@cornell.edu.
authors: Jason W
authors: JW
authors: Locasale
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D045325:HCT116 Cells; D006801:Humans; D055432:Metabolomics; D008810:Mice, Inbred C57BL
chemical_list: D000214:Acyl Coenzyme A