title: Lipidomic profiling of tryptophan hydroxylase 2 knockout mice reveals novel lipid biomarkers associated with serotonin deficiency.
abstract: Serotonin is an important neurotransmitter that regulates a wide range of physiological, neuropsychological, and behavioral processes. Consequently, serotonin deficiency is involved in a wide variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, schizophrenia, and depression. The pathophysiological mechanisms underlying serotonin deficiency, particularly from a lipidomics perspective, remain poorly understood. This study therefore aimed to identify novel lipid biomarkers associated with serotonin deficiency by lipidomic profiling of tryptophan hydroxylase 2 knockout (Tph2-/-) mice. Using a high-throughput normal-/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF-MS) method, 59 lipid biomarkers encompassing glycerophospholipids (glycerophosphocholines, lysoglycerophosphocholines, glycerophosphoethanolamines, lysoglycerophosphoethanolamines glycerophosphoinositols, and lysoglycerophosphoinositols), sphingolipids (sphingomyelins, ceramides, galactosylceramides, glucosylceramides, and lactosylceramides) and free fatty acids were identified. Systemic oxidative stress in the Tph2-/- mice was significantly elevated, and a corresponding mechanism that relates the lipidomic findings has been proposed. In summary, this work provides preliminary findings that lipid metabolism is implicated in serotonin deficiency.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.|Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agriculture Sciences, Beijing, 100081, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Weng
authors.affiliation: Beijing National Laboratory for Molecular Sciences, the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Sensen
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Chemistry and Center for Single Cell, Single Nanoparticle, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO, 65409, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: Burton
authors.affiliation: Beijing National Laboratory for Molecular Sciences, the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Analytical Instrumentation Center, Peking University, Beijing, 100871, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Nie
authors.affiliation: Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
authors.forename: Yonglu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Beijing National Laboratory for Molecular Sciences, the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China. yu.bai@pku.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Beijing National Laboratory for Molecular Sciences, the Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Huwei
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D012701:Serotonin / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008055:Lipids; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase
keywords: Lipid biomarkers; Lipidomics; Serotonin deficiency; Tryptophan hydroxylase 2 knockout (Tph2−/−) mice; Two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry (2D LC–QToF-MS)